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299 Cards in this Set
- Front
- Back
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List the levels of functional organization of the body. What is the basic unit of life?
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Chemical level:
Cellular level: Basic Unit of Life Organ level: Tissue level Body system level: Organism level: |
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Name the 4 primary types of cells/tissues and their main function
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Muscle Cells: Specialized for contraction and generation of force
Nerve cells: Specialized for initiating and transmitting electrical impulses Epithelial cells: exchanging materials between the cell and its environment Connective cells:Connects, supports, and anchors structures together |
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What is homeostasis?
What is the purpose of homeostasis? |
Dynamic steady state of the
constituents in the internal fluid environment. To Maintain a stable internal environment |
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What must the homeostateic control systems be able to do?
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Detect changes
integrate information restore system to "normal" |
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Which homoeostatic contol Opposes initial change?
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negative feedback system
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What are the components of the negative feedback system?
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Sensor: Monitors magnitude of a control variable
Integrator: Compares sensor’s input with a set point Effector: Makes a response to produce a desire effect |
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Which homeostatic system Drives physiological values away from set point or is destabilizing?
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Positive feedback system
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What is the plasma membrane composed of? How thick is it? What are some of its functions?
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~ 10 nm thickness composed of lipids and proteins
Controls movement of molecules between the cell and its environment serving as a permiability barrier |
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What is Intracellular fluid?
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Fluid contained within
all body cells |
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What is extracelular fluid?
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Fluid environment in
which the cells live (fluid outside the cells) |
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What are the two components of the ECF?
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Plasma, interstitial fluid
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What molecules are higher in the ECF?
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Na +, Cl-, HCO3-
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What molecules are higher in the ICF?
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K+, PO4-, Mg 2+, Amino Acids, Proteins
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List componets of plasma membrane...
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Carbohydrates, cholesterol, phospholipids
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What are integral proteins?
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Proteins that are embedded in, and
anchored to, the cell membrane. Can be receptor or gated |
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What are peripheral proteins?
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Proteins that are loosely attached
(not embedded) to either the intracellular or the extracellular side of the cell membrane |
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What describes the movement of water?
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Osmosis
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What describes the movement of particles?
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diffusion
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What is the name of the membrane
proteins that form channels specific for the passage of water? |
aquaporins
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What is Fick’s Law?
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If the solute cannot move, then water must move to
maintain equal concentrations on two sides of membrane |
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A Semi-permeable membrane allows what to move?
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Water
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Osmotic pressure results from/is dependent on?
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results from the difference in water
concentration The osmotic pressure of a solution depends on the concentration of solute particle in solution |
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what is hydrostatic pressure?
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results from gravitational force on a
column of fluid Hydrostatic pressure is what is exerted by a liquid when it is at rest. The height of a liquid column of uniform density is directly proportional to the hydrostatic pressure. |
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What is Osmolarity?
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# osmoles / L solution
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how do you calculate osmoles?
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An osmole is the number of particles into which a solute dissociates in solution.
ex:1 mole CaCl2 = 3 osmoles |
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Isoosmolar:
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having the same osmolarity
as normal extracellular fluid |
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Hypoosmolar:
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having a lower osmolarity
than normal extracellular fluid |
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Hyperosmolar
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having a greater osmolarity than normal extracellular fluid
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What is "g" in an osmolarity equation?
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g = Number of particles per mole in solution (Osm/mol)
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Osmolarity =
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g C
or (# particles/moles in solution) X (solute concentration) |
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What is the osmolarity of a
5 M solution of CaCl2? |
15 osmoles
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What is Effective Osmolarity?
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Refers to those particles that will exert an actual osmotic effect (water movement) on a cell... Non-Permeable solutes
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If two solutions of different effective osmolarity are separated by a membrane only permeable to water, the diffusion of water would occur from:
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the lower osmolarity
solution (higher water concentration) to the higher osmolarity solution (lower water concentration). |
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What happens if there is a higher
concentration of an impermeable substance inside a cell? |
Water is forced to move and cell volume and shape changes (water will move into the cell)
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What is an isotonic solution and what would happen to a cell in an isotonic solution?
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Has same concentration of non-penetrating solutes as normal body cells (290 mOsmoles/L)
Cell volume remains constant |
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What is a hypotonic and what would happen to a cell in an hypotonic solution?
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Lower concentration of non-penetrating solutes
than normal body cells Water will enter the cell and can cause swelling or lysis |
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What is a hypertonic and what would happen to a cell in an hypertonic solution?
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Higher concentration of non-penetrating solutes
than normal body cells Cells could shrink as they loose water by osmosis. |
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What is the physiological Response to Cell Swelling?
What channels are most commonly activated? |
If the extracellular fluid becomes hypoosmolar, water will enter with the osmolar gradient and the cell will swell.
Cell swelling activates solute efflux mechanism – Regulatory Volume Decrease Most commonly the Cl - and K + channels are activated Resultant net efflux of Cl - and K + decreases osmolarity and water diffuses out of the cell Cell volume is restore to normal |
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What is the physiological Response to Cell shrinkage?
What channels are most commonly activated? |
If the extracellular fluid becomes hyperoosmolar, water will leave with the osmolar gradient and the cell will shrink.
Cell shrinking activates solute uptake mechanism – Regulatory Volume Increase Most commonly the Na + /H + exchanger is activated (Na + in /H + out) H + extrusion alkalinizes the cell and activates the Cl - /HCO3- exchanger Resultant net increase in intracellular Na + and Cl - draws water into the cell Cell volume is restored to normal |
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What is flux?
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Rate of diffusion
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What is Efflux, Influx and Net Flux?
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Efflux = Diffusion of a substance out of the cell
Influx = Diffusion of a substance into the cell Net Flux = difference between influx and efflux, identifies the overall direction of flux |
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What variables incresase effect of rate of diffusion?
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increased surface area
increased lipid concentration increased concentration gradient |
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What factors decrease the rate of diffusion?
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increased molecular weight
increased thickness of membrane or distance |
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How does carrier mediated transport work?
Is it active or passive? What characteristics are limiting factors? |
Accomplished by membrane carrier
flipping its shape Both Stereospecificity Saturation Competition |
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How does the rate of transport compare to the extracellular concentration?
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Rate of transport is directly
proportional to the extracellular concentration of the molecule until Tm is reached |
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Flux via mediated transport is
determine by what three factors? |
Number of binding sites
Number of transport molecules Rate of transport |
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What is Tm? Why do we care?
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It is the transport maximum...
It is characteristic of carrier mediated transport processes and indicates the fact that transporters can saturate |
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What is facilitated diffusion?
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Substances move from a higher
concentration to a lower concentration with no ATP |
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Compare Facilitated diffusion with primary active transport in regards to concentration gradients, carrier molecules, and energy consumption
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Facilitated Diffusion:
Substances move following its concentration gradient Requires carrier molecule Does not require energy Primary Active Transport Moves a substance against its concentration gradient Requires a carrier molecule Requires direct use of ATP |
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How much of total body water is in ICF?
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2/3
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How much of total body water is in ECF?
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1/3
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What are the components of ECF and what proportion of the ECF do they make up?
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Interstitial Fluid = 3/4 ECF
Plasma = 1/4 ECF |
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What is the 60-40-20 rule?
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60% of body weight is total body water (ECF & ICF)
40% is ICF 20% is ECF |
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What is the formula for Total Body Water?
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TBW= 0.7(lean body mass in kg) + 0.1 (Adipose tissue in kg)
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how does water content correlate with fat stores/
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Inversely. increased body fat = decreased water %. Women therefore have lower water % due to increased fat content
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If the proportion of lean body mass is not known, how can you determine the total body water. What are the limitations?
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TBW will equal (0.6)x(weight in kg). This will only work if % adipose isn't greater that 20%
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What are two sources for water intake and what is approximate amount?
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Ingested via fluids or foods
~2100 ml/day Produced via oxidation of carbohydrates ~200ml/day |
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Insensible water loss means?
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water lost that you can't sens, like from breathing or diffusion through the skin
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What does interstitial fluid NOT include?
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Plasma and RBCs
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What are the major ions of ISF?
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Na+, Cl- and HCO3-
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What are the major ions if ICF?
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K+, protein anions, and inorganic phosphates (PO4 3-)
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What is the ionic composition of plasma?
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Same as ICF except it does include protein anions.
Na+, Cl-, HCO3- |
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What is BUN?
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blood urea nitrogen; is a measure of the amount of nitrogen in the
blood in the form of urea. Urea is a substance secreted by the liver, and removed from the blood by the kidneys. Therefore BUN is also used as a measurement of renal function. |
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What is the formula for plasma osmolarity?
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2Na + (glucose/18) + (BUN/2.8)
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What is the significance of electrolytes to body water dynamics?
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Electrolytes like Na+ do not cross cell membranes are are confined to the ECF.
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What is the result of Gain of Isotonic (NaCl) Saline Solution?
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Increase in ECF volume
No change in ICF volume Increase in TBW No change in ECF or ICF osmolarity No shift in H2O between ICF and ECF Decrease plasma protein concentration and hematocrit (diluted because of increase in ECF) |
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What is the result of Loss of Isotonic Fluid, like from diarrhea, vomiting, etc?
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Decrease in ECF volume
No change in ICF volume Decrease on TBW No change in ECF or ICF osmolarity No shift in H2O between ICF and ECF Increase plasma protein concentration and hematocrit (concentrated because of loss in ECF) |
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What is the result of Gain of Hypotonic Solution, like from (e.g. drinking pure water, SIADH -syndrome of inappropriate anti-diuretic hormone secretion)
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Increase in ECF and ICF volume
Increase in TBW Decrease in ECF and ICF osmolarity Shift in H2O from ECF to ICF Decrease plasma protein concentration No change in hematocrit Concentration of RBC decreases with dilution RBC volume increases because of water shift into RBCs |
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What is the result of Loss of Hypotonic Solution such as with excessive sweating or water deprivation?
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Decrease in ECF and ICF volume
Decrease in TBW Increase in ECF and ICF osmolarity Shift in H2O from ICF to ECF Increased plasma protein concentration No change in hematocrit Concentration of RBC increases with fluid loss RBC volume decreases because of water shift out of RBCs 28 |
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What is the result of High NaCl intake?
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Increase in ECF volume and osmolality
Decrease in ICF volume Increase in ICF osmolality No change in TBW Shift in H2O from ICF to ECF Decrease plasma protein concentration and hematocrit (diluted because of increase in ECF) |
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What is the result of loss of sodium such as with Aldosterone Insufficiency?
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Decrease in ECF volume and osmolality
Increase in ICF volume Decrease in ICF osmolality No change in TBW Shift in H2O from ECF to ICF Increase plasma protein concentration and hematocrit (concentrated because of loss in ECF) |
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What is the result of an Isotonic Glucose Infusion?
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Increase in ECF and ICF volume
Increase in TBW Decrease in ECF and ICF osmolarity Shift in H2O from ICF to ECF Decrease plasma protein concentration and hematocrit (diluted because of increase in ECF volume) Concentration of RBC decreases with dilution RBC volume increases because of water shift into RBCs |
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What happens with SIADH?
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In SIADH, inappropriately high levels of ADH are secreted
Excess water is added to the ECF and ICF (in proportion to original values) ECF and ICF volume increased ECF and ICF osmolarities decreased Plasma protein concentration is decreased, by dilution Hematocrit unchanged RBC volume increases because of H2O shift in them. |
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What is SIADH?
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Syndrome of Inappropriate Anti-diuretic Hormone Secretion
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Give example of causes of Isosmotic volume contraction
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-diarrhea
-burn |
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Give example of causes of Hyperosmotic volume contraction
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-sweating
-fever -diabetes insipidus |
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Give example of causes of Hyposmotic volume contraction
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-aldosterone deficiency
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Give example of causes of Isosmotic volume expansion
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-NaCl infusion
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Give example of causes of Hyperosmotic volume expansion
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-High NaCl intake
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Give example of causes of Hyposmotic volume expansion
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-SIADH
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What separates ECF from ICF?
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The cell membrane
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What separates ISF from Plasma?
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the capillary wall
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What is the charge inside a cell?
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negative
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What is the charge outside a cell?
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positive
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What does the magnitude of a membranes potential depend on/
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the number of opposite charges separated... the greater the number of charges separated, the greater the potential
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Which crosses the cell membrane more easily, K+ or Na+? Why?
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K+
The cell has many more channels open for passive K+ traffic than for Na+ traffic and is 50-75x more permeable to k then na |
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What is the approximate intracellular concentration of Na+ and K+?
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Na+ 15mM
K+ 150mM |
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What is the approximate extracellular concentration of Na+ and K+?
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Na+ 150mM
K+ 5mM |
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What are bacground channels
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channels open in the absence of stimuli, baseline channels
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True or False: There are many types of ion channels, even for the same ion
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true
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Chemical driving force for diffusion is caused by:
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concentration gradient across a membrane
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Electrical driving force for diffusion is caused by:
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separation of charges across a membrane
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What are the two requirements for development of diffusion potentials:
How are DP created |
1)different concentrations of ions inside and outside of cells
2)selective permeability of the membrane DP are creat3ed by movement of only a few ions and do not cause changes in concentration |
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What are the 4 tyoes of diffusion potentials
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Equilibrium potentials
resting membrane potentials graded potentials action potentials |
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define equilibrium potential
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the diffusion potential (electrical) that exactly opposes or balances the tendency for diffusion down a concentration gradient such that chemical and electrical forces are in equal and opposite directions
determined by a given set of ion concentrations |
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What is the Nernst Equation used for and what is the equation?
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it is used to calculate the equilibrium potential for an ion at a given concentration (assuming the ion is permiable to the membrane)
Eion= (60/[ion charge])log([ion]ECC/[ion]ICC) |
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What is the Equilibrium potential of Na+
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+65mV
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What is the Equilibrium potential of K+
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-90mV
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What is the Equilibrium potential of Cl-
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-90mV
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What is the Equilibrium potential of Ca2+
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+120mV
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What is resting membrane potential?
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the difference that exists across the membrane of excitable cells at steady-state (ex nerve and muscle cells that have ability to have transient change in membrane potential when excited).
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What is the resting membrane potential of a "typical" cell. Why is it that number?
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-70mV
the Ek+ is =-90mV inside and hte ENa+ is = +65 outside, but since the membrane is more permeable to K+ it has the dominant effect on the cell, bringing the resting potential to roughly -70mV, closer to the Ek+ |
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What does Ohm's Law measure?
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the membrane potential knowing equilibrium potentials and conductance for each ionic species present
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What does g= ?
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conductance, ot the number of channels open for a particular ion
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what is Eion dependant on
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the concentration gradient of Ion(in) and Ion(out) (from nerst equations)
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What is the formula for ohms law?
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Em=
(gkEk +gNaEna+gClECl+gCaECa) _____________________________ (gK+gNa+gCl+gCa) |
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If k+ channels open with no change in concentration gradients or any other properties what happens to Ememb?
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It becomes more negative and closer to EK
The cell is hyperpolarized |
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What happens to the RMP of a cell in a patient who is severly hypokalemic? Will this cause hyperpolarization or depolarization?
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The gradient for K= increases causing Ek to be more negative which causes the RMP to be more negative. Causes Hyperpolarizarion
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If muscle cells have a hyperpolarized RMP, what how might that patient present?
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Paralysis, suffocation, asystole
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What happens to the RMP of a cell in a patient who is hyponatremic?
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The gradient for Na+ decreases causing ENa+ to become more negative.
The ENa+ change is minimal since Na+ is less permiable. RMP is not appreciably changed. |
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Increased ECF K+ is called:__________ and leads to what membrane potential change?
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Hyperkalemia
Depolarization |
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Increased ECF Na+ is called:__________ and leads to what membrane potential change?
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Hypernaturemia
Depolarization |
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Decreased ECF K+ is called:__________ and leads to what membrane potential change?
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Hypokalemia
Hyperpolarization |
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Decreased ECF Na+ is called:__________ and leads to what membrane potential change?
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Hyponatremia
Hyperpolarization |
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Decreased ICF K+ yeilds
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depolarization
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Decreased ICF Na+ yeilds
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depolarization
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Increased ICF K+ yields
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hyper-polarization
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Increased ICF Na+ yeilds
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hyper-polarization
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where is the impulse generating and conducting region of a neuron
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Potential starts in the axon hillock and is generated and conducted in the axon
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What are graded potentials?
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transient electrical signals that travel short distances
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What are action potentials?
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Self-replicating transient electrical signals that can travel long distances
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What does the RMP depend on?
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Permeability and Electrochemical gradients established by conductance of K+ and NA+
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What is polarization
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any state where membrane is other than 0mV
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What is depolarization?
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When the membrane is LESS polarized than at resting potential. (-69, 0, +35)
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What is re-polarization?
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When the membrane returns to resting potential after having been depolarized
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Hyperpolarization
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when the membrane becomes more polarized than at resting potential (EX -71,
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What are some triggering events that can produce changes in membrane permeability?
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Change in electrical Field
interaction of chemical messenger with surface receptor stimulus imbalances in leak-pump cycle |
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What are the four major basic categories of channels?
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Ligand-Gated
Voltage Gated Mechanosensitive Background |
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What causes ligned gated channels to open? What do they generate?
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Chemical signals. They generate graded potentials.
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How do voltage gated channels open? What do they generate?
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they have voltage sensors that alter the conformation of the channel if the membrane potential reaches a certain range.
They initiate action potentials. |
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How do mechanosensitive channels work? What do they generate?
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they respond to membrane deformation, touch, and other sensory inputs like from sound, blood pressure, etc.
Graded potentials |
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How do background channels work? What do they generate?
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spontaneously open, don't need stimuli
maintain resting membrane potential |
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7 Characteristics of Graded Potentials
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Occurs in small specialized region of membrane
produced by local changes in MP Can be depolarizing or hyperpolarizing Vary in amplitude and duration bidirectional, decremental conduction Change in potential proportional to stimulus |
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Explains Steps to Graded Potentials
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RM exposed to chemical stimulus
Chemical/ligand channels open Membrane depolarizes or hyperpolarizes Movement of ions causes local current moving outward Can lead to action potentials |
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What are EPSPs? What do they do? What channel type? Give an example
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Excitatory postsynaptic potentails:
Usually depolarizing, bringing membrane potential closer to threshold Opening of MIXED-Cation channels (K+out and Na+ in) ACh receptors |
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What are IPSPs? What do they do? What channel type?
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Inhibitory postsynaptic potentails:
Usually hyperpolarizing, bringfurther from threshold Opening of EITHER- K+ (in) or Cl- (out) channels |
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Current flow direction is designated by what charges?
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Positive
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4 Examples of Graded Potentials
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Postsynaptic Potentials
End-Plate Potentials Pacemaker Potentials Slow-Wave Potentials |
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What is a GPSP
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A Grand Postsynaptic Potential that is a compositie of all the EPSPs and IPSPs occuring at approximately the same time.
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What is temporal summation?
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the summation of several EPSP's occurring very close together in time by successive firing of a single presynaptic neuron
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What is Spatial Summation?
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summation of several EPSP's occuring simultaneously from SEVERAL different presynaptic inputs
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What is the importance of postsynaptic neuronal integration?
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It allows for integration od EPSP's and IPSP's so that a fine degree of discrimination and control in determining what information will pass on.
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How are signals conducted through a neuron?
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Dendrites receive signals from other neurons through ligand gated (graded) channels
If depolarization occurs to a certain point, an action potential is created in the axon hillock The conducting zone conducts the AP over long distances undiminished Axon terminals are stimulated to release neurotransmitter that influences other cells |
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Describe voltage gated Na+ channels
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Stimulated to open by AP
Has activation gate & Inactivation gate At threshold triggered for rapid opening and slow closing; inactivation gate must be reopened before channel can be capable of opening again. |
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Describe voltage gated K+ channels
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Stimulated to open by AP
Has only one gate which is open or closed delayed opening triggered at threshold |
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What repolarizes the membrane to its resting state after and AP?
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K+ channels that are opening as sodium channels become inactive
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How does depolarization of occur (in regards to an AP)?
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Na+ channels open at threshold and during depolarization via positive feedback reversing membrane potential from -70mV to +30mV.
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Name the poision in puffer fish and explain how that toxin and lidocaine both work.
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Tetrodotoxin TXX
Both inhibit voltage gated NA+ channels preventing the occurrence of AP |
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What is accommodation? When can it occur?
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A cell is less likely to fire because sustained depolarization closes the inactivation gares on the Na+ channels even though the cell membrane is closer to threshold. Occurs in hyperkalemia (elevated serum k+levels).
The property of a nerve by which it adjusts to a slowly increasing strength of stimulus, so that its threshold of excitation is greater than it would be were the stimulus strength to have risen more rapidly. |
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What is an important effect of depolarization?
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It closes the inactivation gates on Na+ channels so that no AP can be generated even if activation gates are open. No AP=no muscle contraction
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How does the diameter of a fiber determine the speed of conductance?
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the larger the diameter, the lower the resistance, the faster the conduction
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How does the mylenation of a fiber determine the speed of conductance?
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mylenation increases legnth constant and decreases capacitance
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What is the time constant
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how quickly a membrane can respond to a current
time=membrane resistance/internal resistance |
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what is the legnth constant?
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how far a depolarizing current will spread.
legnth=sqrt(membrane resistance/internal resistance) |
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What is contiguous conduction?
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"touching" conduction where AP spread along whole umylenated fiber
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What is saltatory conduction?
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"jumping" conduction where AP jumps over myelenated sections of nerve fiber...Very fast 50x faster than similar unmylenated fiber
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What make myelin and what is it composed of?
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Lipids
Made by oligodendrocytes in CNS and Schwann Cells in PNS |
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What is MS?
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Multiple Sclerosis
myelin is destroyed and nerve conduction ceases (no voltage gated channels where mylenation was) |
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What is Lambert-Eaton Syndrome?
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an autoimmune disorder caused by antibodies that attack the
presynaptic voltage-gated Ca 2+ channel resulting in a reduction in depolarization-induced influx of Ca 2+ for neurotransmitter release. Lambert-Eaton syndrome is most often seen in patients with certain types of cancer, such as small cell lung carcinoma. |
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What enzyme makes acetylcholine and where is it found?
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choline acetyltransferase (using choline and acetyl CoA)
found in nerve terminal |
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What enzyme breaks down cetylcholine and where is it found?
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acetylcholinesterase, found in snaptic cleft breaking it into chiline and acetate
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what snare senses increased Ca2+?
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synaptotagmin
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Name Common neurotransmitters
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Acetocholine
norepinpherine, epinepherine and dopamine (from tyrosine) serotonin histamine glutamate glycine GABA Nitric Oxide |
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What are the characteristics of neurotransmitters?
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small, rapid acting, synthesized and packaged into synapic veessicles at TERMINAL, always the same one released at a particular synapse, quickly removed
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What are the characteristics of neuropeptides?
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large molecules, slow, prolonged response
synthesized in the cell body by rer/golgi and moved to terminal called dense core vessicles in axon terminal undergo Ca2+ induced exocytosis and release neuropeptides when NT are released act as neuromodulators |
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what are neuromodulators
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chemical messengers that fon't form EPSPs or IPSPs but rather depress or enhance the action of a synapse subtly and longer term
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Examples of Neuropeptides:
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ACTH (Adrenocorticotropin)
TRH (thyrotropin releasing hormone) Endorpins Vasopressin glucagon oxytocin, secretin, substance P |
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Receptors that are ION gated are referred to as:
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ionotropic receptors
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Receptors that are coupled to G proteins are referred to as:
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metabotropic receptors
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Activation of ionotropic receptors causes:
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rapid opening of ion channels. This channel activation in turn results in depolarization or hyperpolarization
of the postsynaptic membrane, the choice depending on the ionic selectivity of the conductance change. |
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Activation of metabotropic receptors causes:
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G protein-linked receptor activation: results in the production of active α and βγ subunits, which initiate a wide variety of cellular responses by direct interaction with either ion channel proteins or other second-messenger effector proteins.
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What is Physiological modulation of synaptic transmission?
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The normal regulation of
synaptic transmission. the altering of pre-synaptic and postsynaptic factors that can aid in facilitation or inhibition. Presynaptic facilitation or inhibition is more common |
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What are some possible synaptic drug interactions?
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(A) Increase leakage of
neurotransmitter from vesicle to cytoplasm, exposing it to enzymatic breakdown (B) Increase transmitter release into the cleft (C) Block transmitter release (D) Inhibit transmitter synthesis (E) Block transmitter reuptake (F) Block cleft enzymes that metabolize the transmitter (G) Bind to receptor on postsynaptic membrane to block (antagonist) or mimic (agonist) transmitter action (H) Inhibit or stimulate second messenger activity within the postsynaptic cell |
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What tyes of channels are found at sarcolemma
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voltage gated channels
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what type of channels are found on motor end plate?
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chemically gated channels
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What is synaptobrevin?
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synaptic vesicle protein
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What are syntaxin and SNAP-25?
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plasma-lemma associated proteins
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what is synaptotagmin?
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a snare protein located on the vessicle that senses calcium
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How many Ach molecules does it take to open a ACh receptor? What does channel open to?
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2
one binds and conformational change allows sencond Ach to bind Channel that is opened allows for K+ and Na+ to move through |
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What are MEPP's
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they are minature end plate potentials caused by the relase of ACh. Summation of several MEPP's produce and EPP which is localized at the motor end plate
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What is the margin of safety?
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it is the "buffer" of stimulus provked by the EPP and what is actually required to initiate an action potential. It allows/helps prevent failure at the neuromuscular junction, particularly if there are competing toxins, etc.
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What are the steps in the Neuromuscular Transmission?
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1. action potential in the ! -motor neuron
2. Ca 2+ through voltage-gated channels 3. Ach vesicle migration and fusion 4. Ach release into the synaptic cleft 5. binding of Ach to the Ach receptor and Na + influx 6. End plate potential 7. if threshold is reached opening of voltage-gated Na + channels and depolarization of the sarcolemma 8. Degradation of acetylcholine by acetylcholinesterase (AChE). |
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What is tubocurarine (curare)?
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A non-depolarizing drug that competitively blocks (ANTAGONIST) binding of Ach to receptors causing paralysis
Used during surgery as a adjunct to but not as a replacement for anesthesia. |
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What is succinylcholine?
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A drug that depolarizes the sarcolemma of the muscle fiber and prevents further activation of the muscle
- used to induce muscle relaxation and short term paralysis, usually to make endotracheal intubation possible. |
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Botulism toxin does what?
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degradation of synaptobrevin, SNAP-25, or syntaxin, depending on the toxin type
-prevents fusion of synaptic vesicles -target: neuromuscular junction and cholinergic nerve endings in ANS -flaccid paralysis and death via respiratory paralysis -used clinically to treat many conditions, e.g. muscle spasms |
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What happens with Anticholinesterase poisoning
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Inhibit acetylcholinesterase
-pesticides and many nerve gases -Ach accumulates in the synaptic cleft -prolongs action of Ach -depolarizing muscle block -initially muscle fasciculations -followed by muscle weakness -receptor desensitization -possibly by a conformational change in the receptor -also used medically |
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What happens with Myasthenia Gravis?
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Circulating antibodies block Ach
receptors: • EPP decreases • decreased margin of safety • recruitment declines with use; some motor units fail to reach threshold due to decreased margin of safety • treated with cholinesterase inhibitors |
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What is neostigmine:
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prolongs and enhances action of ACh at motor end plate
• It is used to improve muscle tone in people with myasthenia gravis (reduced number of available Ach receptors. • In anesthesia at the end of an operation, to reverse the effects of non-depolarizing muscle relaxants |
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Levels of skeletal muscle organization
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whole muscle
fasicle (bundle of fibers) muscle fiber/cell myfibril hyofilament |
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Describe muscle fibers
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large (~90um) and multinucleate
composed of bundles of myofibrils |
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What do t-tubules contact
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the terminal cisternae of the sarcoplasmic reticulum
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what is the function of the sarcoplasmic reticulum?
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Ca2+ storage inside a muscle fiber
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How is Calcium from the Sarcoplasmic reticulum released to aid in muscle contraction?
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1) Depolarization of T Tubules causes a conformational change in the the DHP (L-type) recepros that mechanically open the Ryanodine receptor (RYR or calcium release channel) to open
2)Ca2+ exits the SR via the Ryanodine channek and activates troponin c leading to muscle contraction |
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What are the three parts of the triad?
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SR cisterna, T Tubule, SR Cisterna
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What are myfibrils made of?
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bundles of myofilaments
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What are the two types of myofilaments
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Thick Myosin and Thin Actin
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Describe a thick filament
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it is two proteins twisted together and called "myosin"
the two heads are called the cross bridge and the remainder is called the tail |
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What filament type has ATPase activity?
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myosin
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What is the significance of myosin in uncontrolled diabetics?
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It is subject to glycation and can alter muscle function
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What is an actin filament composed of
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it is composed of three proteins:
1)Globuklar actin which forms F-actin, a two stranded helical structure 2)tropomyosin 3)troponin |
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What is the function of tropomyosin?
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inhibits bingind of myosin to actin
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What is the function of troponin?
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Ca2+ sensitive molecule that changes conformation in presence of Ca2+ to move blocking tropomyosin
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What is the function of TnC?
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troponin calcium:
calcium sensor that causes conformational change in TnI |
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What is the function of TnT?
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links Troponin to Tropomyosin to contol the position of Tm on the thin filament
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What is the function of TnI?
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troponin I:
binds to actin and inhibits myosin ATPase |
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What is the smallest contractile unit of muscle?
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the sarcomere composed of organized myofilaments
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What is the function of Titan
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stabilizes myosin filaments in the longitudinal axis
largest known protein |
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What is the function of nebulin
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protein "ruler"that regulates the legnth of the actin filaments
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How many thin filaments per thick filament?
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6 thin to 1 thick
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What is the function of dystrophin?
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it connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane
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What is muscular dystrophy
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abnormalities in the gentes that code for dystrophen. syndrome characterized by muscle wasting and weakness
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What is the sliding filament theory?
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states that contraction occurs by the sliding of thin filaments past the thick in a seres of cyclic reations between the myosin head and the actin filaments that resluts in teh musce shortening
contractile forece proportional to the nyosin/acting interactions |
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What happens to the sarcomere during contraction?
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it shortens
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What does myosin look like at rest?
Actin? |
Myosin head holds ADP and Pi
Binding site on actin blocked by Tm/Tn complex |
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What are the steps in the cross bridge cycling?
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AP causes release of Ca+ from SR
Ca2+ binds to TnC, exposing myosin binding site myosin binds to acin Pi release initiates powestroke, myosin head shifts, ADP is relased ATP binds with myosin releasing it from actin and hydrolyzing into ADP-Pi complex Conformational shift of myosin head back to energized state |
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What is SERCA?
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SERCA resides in the sarcoplasmic reticulum (SR) within muscle cells. It is a Ca2+ ATPase that transfers Ca2+ from the cytosol of the cell to the lumen of the SR at the expense of ATP hydrolysis during muscle relaxation.
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What is calsequestrin?
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Calsequestrin, binds calcium within the SR and helps to reduce the concentration of free calcium within the SR, which assists SERCA so that it does not have to pump against such a high concentration gradient.
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What is Malignant Hypothermia
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Autosomal dominant disorder that is triggered by anesthetics linked to gene in ryanodine receptor and possible a mutation in calsequestrin.
causes skeletal muscle contraction without an AP and causes ha hypercatabolic state. Tx: dantrolene sodium that is a muscle relaxer |
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What is tetanus?
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when a muscle fiber is stimulated so rapidly that it does not relax at all between stimuli, a smooth, sustained contraction occurs
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What is summation?
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the increased frequency of stimulation in a motor unit that results with successive contractions with increasing forces :piggybacking" on each other to yield a maximal contraction
(tetanus can occur) High frequency keeps cytosolic Ca2+ high |
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What is the effect of high ionized or "free" calcium? How might this present?
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Ca2+ will bind to nigative sites on phospolipids making the membrames more stable and less exciteable
thershold potential becomes less negative and a larger stimulus would be required to generate an AP Muscle weakness would be a symptom |
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What is the effect of low ionized or "free" calcium? How might this present?
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Threshold becomes more negative and the neuron becomes mroe excitable
Muscle twitching would be a symptom of enhanced excitability |
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Describe the plasma concentration oc Ca+
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50% free (ionized)
50% bound (40% bound to plasma proteins, 10% bound to small anions like phosphate, citrate and bicarbinate) |
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If plasma concentration of phosphate decreases, what happens to free calcium levels and what is the effect on the neuron. What condition can cause this
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increase in free Ca2+
Reduce neuron excitability hyperparathyroidism |
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If plasma concentration of phosphate increases, what happens to free calcium levels and what is the effect on the neuron? What condition can cause this.
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decrease in free Ca2+
Increase neuron excitability hypoparathyroidism |
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What do the parathyroid glands do?
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They produce parathyroid hormone, which controls calcium, phosphorus, and vitamin D levels within the blood and bone.
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What is the effect of acidemia on free calcium levels/neurons?
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excess H+ will bind to albumin leaving fewer sites for Ca2+
Increase free calcium decrease neuron excitability |
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What is the effect of alkalemia on free calcium levels/neurons?
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deficit of H+ ions causes more Ca2+ to bind to albumin
decreases free calcium increases neuron excitability |
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Isometric contractions characteristics
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measured when length is held constant
no shortening however the muscle is still stimulated to contract |
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Isotonic contraction characteristics
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measured when load is held constant
muscle contracts against the load and shortening is measured |
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A sarcomere runs from
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Z line to Z line
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What is present in the A band
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thick filaments (total legnth)
however there is overlap of the thin filaments here |
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where are thin filaments anchored
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the z line
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What is present in the I band
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thin filaments
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Motor neuron + innervated fibers =
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motor unit
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What is recruitment in the muscle?
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progressive activation of additional motor unit so that increased recruitment = increased force production
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What is the "all or none" principal form muscle fibers
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in reference to individual muscle fibers
all fibers in a motor unit will contract when the motor neuron is innervation these fibers is stimulated |
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What is graded activation of muscle
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in reference to the whole muscle
not all motor units are activated at one time and graded muscle force development is due to recruitment of motor units and summation |
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Describe Type I Fibers
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Marathon Runner Profile
"DARK" High mitochondria small fiber size slow contractile speed low power high endurance hig aerobic activity high myoglobin |
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Describe Type IIa Fibers
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Sprinter Profile
"Light" lower mitochondria larger fibers predominate (more myosin) fast contractile speed high power low endurance high SR content High ATPase content Anerobic activity |
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Describe Type IIx Fibers
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really fast fibers, rarely seen in healthy humans
seen in spinal cord injuries bed rest or extreme athletes |
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What do the following set?
Myobifrillar volume SR Volume Mitochondrial Volume |
Force generate = MF Vol
Frequency = SR Aerobic ATP synthesis rate = Mito vol |
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What is muscle hypertrophy
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occurs later in training where an increase in the size of the muscle fiber increases muscle strength
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What is the process of how muscles get bigger?
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Mechanical stimulis activates protein signaling cascade which increases gen activation within hours of exercise which causes increase protein synthesis and muscle growth within hours and days
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What is sarcopenia?
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the degenerative loss of skeletal muscle mass and strength with aging due to reduced fiber size
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What fiber type do older individuals rely more heavily on?
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Type 1
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What are the implications of inactivity or bed-rest on the muscles
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~20% loss of muscle mass can occur in the first month!
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What are the three divisions of the ANS and what do they do?
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Sympathetic: Fight or Flight
Parasympathetic: Rest/Digest Enteric: "Gut Brain" |
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Compare Autonomic to Somatic nervous systems...
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ANS
Smooth muscle, cardiac, glands Tissues inhibited or stimulated Two synapses: 1 ganglia, 1 target organ pregang mylenated, post unmylenated NT: ACh, NEpi Receptors: nicotinic, muscarini and adrenergeric SNS Skeletal Muscle Movement of SM 1 Neuron cell bodies live in ventral horn of spinal cord only 1 synapse all mylenated NT-Ach only Receptor: Ach or nicotinic |
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What are the NTs of the ANS?
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Acetocholine for parasympathetic
norepinepherine for sympathetic |
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What are the NTs of the SNS?
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only acetylcholine
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The adrenal medulla is part of which system and what does it do?
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part of the sympathetic nervous system of the ANS. It is a modified sympathetic ganglia that triggers release of nor-epineptheine (20%) and epinephrine (80%)
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What are the two major NT for the sympathetic and parasympathetic systems?
What are their corresponding nerves called? |
Ach & NE
nerves that use ACh are cholinergeic nerves nerves that use NE are adrenergic |
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What nerves release Ach?
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All sympatheic and aprasympatheic preganglionic nerves
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What nerves release NE?
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Most sympathetic postganglionic
and the adrenal medulla |
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What is the receptor for preganglionic sympathetic
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nicotinic
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What is the receptor for postganglionic sympathetic
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Adrenerergic a1, a2, b1,b2
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What is the receptor for preganglionic parasympathetic NT's?
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nicotinic
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What is the receptor for postganglionic parasympathetic NT's?
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muscarinic
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What are chatecholamines?
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hormones like Epinepherine, norepinepherine and dopamine that are part of the sympathetic nervous system
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What is the hormone of the parasympathetic nervous system?
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ACh
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Acetylcholineesterase inhibitors are use to treat what conditions
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glaucoma, increase GI motility, myasthenia gravis
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How is Norepinepherine synthesized?
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Tyrosine enters nerve termina, ->converted to DOPA->Converted todopamine->converted to Norepinepherine
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How is norepinepherine uptaken in the presynaptic neuron?
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by the uptake pump 1 mechanism
metabolized by MAO-Monoamine oxidase the uptake pump 1 is inhibited by cocaine and tricyclic antidepressants |
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How is norepinepherine uptaken in the postsynaptic neuron?
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by the uptake pump 2 mechanism
the uptake pump 2 is not inhibited by cocaine. Metabolized by COMT, catechol-O-methyltransferase |
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What are some common cooperative effects of SNS and PNS?
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Salivation
Lacrimal secretion Male sexual response |
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What regins of the CNS are involved in controlling autonomic activities?
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Hypothalimus integrates autonomic, somatic and endocrine information
Medulla is responsible for autonomic OUTPUT Some autonomic reflexes integtated at spinal cord |
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What is an agonist?
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binds to same receptor as NT and elicits the same effect
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what isi an Antagonist?
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binds to receptor and blocks NT's response
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What is The nucleus of the solitary tract?
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The portion of the medulla that is considered the coordinating center od the ANS
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Why is smooth muscle smooth? how else does it vary from skeletal muscle?
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b/c there are no striations, t-tubules, and they are not arranged in sarcomeres
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What are caveolae?
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membrane lipid rafts that provide
means for extracellular communication in smooth muscle |
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How are actin fialments different in smooth muscle?
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they lack troponin
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what are intermediate filaments in smooth muscle?
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filaments that hold dense bodies in shape and provide the cytoskeltal framework of the cell but do NOT directly partcipate in contraction
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Where is Single Unit Smooth Muscle Found?
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GI, Bladder, small blood vessles, and ureter
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Where is MultiUnit Smooth Muscle Found?
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walls of large BV
small airways in lungs Eye base of hair follicle (goosebumps) Vas Deferens |
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What are the characteristics of Single Unit Smooth Muscle?
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They are myogenic (self ecxitable)
they contract as a single unit in coordinated fasion by communucating by gap junctions contraction is slow and energy efficient |
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What are the characteristics of MultiUnit Smooth Muscle?
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Densely innervated by the AND
no electrical coupling between cells behaves as separate motor units so each unit must be stimulated for nerve to contract |
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cross bridge cycling in smooth muscle occurs on what filament?
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the thick myosin filament
(different than skeletal!) |
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what is the RMP on smooth muscle cells
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vairable -65mV to -45mV
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What is the action potential dependent on in SMOOTH muscle?
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Calcium- however only in single unit as multiunit don't fire AP
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a slow wave potential is...
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a membrane potential that cycles between depolarizations and repolarizations resulting in bursts of action potentials (multople
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Pacemaker potential is..
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membrane potential gradually depolarizes until it reaches threshold for firing a single action potential.
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What prevents actin and myosin
from binding at the cross- bridges in the resting state in smooth muscle? |
lightweight proteins called "myosin light-chains"
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What are the Excitation-contraction steps in smooth muscle?
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Increase in cytosolic calcium.
Calcium binds to calmodulin in cytosol. Calcium-calmodulin complex binds to and activates the enzyme myosin light-chain kinase (MLCK). MLCK uses ATP to phosphorylate myosin cross- bridges, enhancing their ATPase activity. Phosphorylated myosin cross-bridges bind to actin filaments. Cross-bridge cycle produces tension and shortening. Power stroke – release of ADP-Pi from myosin head. Cross-bridge detachment requires ATP. Decreased in cytosolic calcium to basal levels promotes activation of the enzyme myosin light-chain phosphatase (MLCP). MLCP dephosphorylates myosin cross-bridges. Dephosphorylated myosin cross-bridges cannot bind to actin filaments. Relaxation occurs. |
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Contraction of smooth muscle is regulated by what filament?
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Thick
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What is the sequence of excitation-contraction coupling in smooth muscle?
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1) action potential in smooth muscle membrane
2) opening of voltage-sensitive Ca2+ channels 3) ICF levels of Ca2+ rise (due mostly to Ca2+ from the ECF and only a little from SR) 4) Ca2+ binds to calmodulin and activates it 5) Ca2+-calmodulin binds to myosin light chain kinase and activates it 6) Myosin is phosphorylated and forms the cross-bridge with actin 7) dephosphorylation of myosin causes latch-bridge formation |
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Compare phasic and tonic contraction
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Phasic contraction is twitch-like shortening followed by relaxation
Tonic contraction is where the force is sustained for very long periods. The ability to maintain force of contraction with decreased numbers of activated crossbridges greatly reduces the amount of energy consumption (ATP turnover) |
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What are Slow waves (pacemaker waves)
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Slow waves (pacemaker waves) – low oscillation of RMP- do not reach threshold unless strong enough - if slow wave potential reaches threshold (~ -35 mV) - trains of action potentials are generated – rhythmical contraction
Slow waves aren't AP's but generate AP's. They are controlled by the interstitial cells of Cajal |
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What is latch-bridge formation?
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In smooth muscle even when Ca2+ levels are low myosin and actin don't detach or detach very slowly. It is caused by dephosphorylation of myosin
This is a called a latch-bridge formation and it causes tonic tension while reducing ATP consumption |
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What is the structure of smooth muscle?
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Actin filaments radiate from dense bodies; ends overlapping myosin filaments interspersed in between actin
Dense bodies attached to one another by intracellular protein bridges; serve as “Z disks” Lacks troponin complex, not striated |
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What are the different ways to decrease ICF levels of Ca2+ in smooth muscle?
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Return of calcium into the SR by a SR Ca 2+ ATPase.
Extrusion of calcium out of the smooth muscle cell by: 1) Sarcolemmal Na + /Ca 2+ exchanger 2)Sarcolemmal Ca 2+ ATPase |
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What are the different ways to increase ICF levels of Ca2+ in smooth muscle?
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Voltage-gated Ca 2+ channels
(Action Potentials) Ligand-gated Ca2+ channels (Hormones and NTs) IP3-gated sarcoplasmic reticulum Ca2+ channels (Hormones and NTs) |
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3 mechanisms by which smooth muscle tone can be regulated
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Block Ca2+
Open potassium increase cAMP to inhibit MLCK |
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What is Basal tone?
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An Intrinsic property of the single-unit smooth muscle
(myogenic). The cytosolic calcium concentration is sufficient to maintain a low level of cross-bridge cycling. |
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What muscle types are troponin found?
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skeletal and cardiac only
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What muscle types are tropomyosin found?
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skeletal, smooth and cardiac
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What molecule is responsible for teatnus?
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Ca2+
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What NT is inhibitory?
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GABA
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