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127 Cards in this Set
- Front
- Back
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____ is basic living unit of body
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cell
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Describe the Functional Organization of the Human Body
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Cell is basic living unit of body
Organs composed of many different cells Each type of cell is adapted to perform particular functions App. 100 trillion cells in human body Cells differ but have basic similar characteristics Almost all have ability to reproduce |
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Extracellular fluid “internal environment
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App. 60% of adult body is fluid
Most intracellular (2/3) About 1/3 extracellular (outside cells) ECF in constant motion Transported in circulating blood Mixes between blood and tissue fluids by diffusion Contains ions & nutrients needed to sustain cell life Cells of body live in same environment (ECF known as internal environment) |
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What is in ECF?
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Sodium
Chloride Bicarbonate Oxygen Glucose Fatty acids Amino acids CO2 |
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What is in ICF?
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Potassium
Magnesium Phosphate |
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Mechanisms of homeostasis
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ECF circulatory system
Nutrients in ECF Removal of metabolic waste products Regulation of body functions Reproduction |
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ECF transport and mixing
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1st ECF moves thru body in blood vessels
2nd fluid moves between capillaries and intercellular spaces between tissue cells All blood circulates average of once per minute Up to 6 times/min during exercise Continual exchange of ECF occurs between plasma of blood and interstitial fluid in intracellular spaces ECF continually mixed – homogeneity of ECF throughout body |
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Systems that contribute to nutrients in ECF
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Respiratory
O2 into blood from alveoli GI tract Carbohydrates, fatty acids, amino acids absorbed into blood Liver Modifies substances for use by other cells/organs Musculoskeletal Moves you to table to eat! Allows you to move to safety from adverse environments |
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Removal of metabolic end products
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CO2 by lungs
Flow thru kidneys removes urea, uric acid, excess ions and water not needed by body |
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Regulation of body functions
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Nervous system
Sensory receptors detect state of body and environment Signals thru motor output of nervous system to cause effect |
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_____ ______ _______ subconsciously controls internal organs
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Autonomic nervous system
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____ via ECF thru out body to regulate body functions
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Hormones
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Regulation of O2 and CO2 in ECF by stimulation of ________ & excitation of respiratory center
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chemoreceptors
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Regulation of B/P by stimulation of ________in carotids and aorta
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baroreceptors
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ECF constituents kept within narrow normal range
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CO2 35-45 mm Hg
pH 7.3-7.4 Na+ 138-146 mmol/L K+ 3.5-5.0 mmol/L |
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Characteristics of control systems
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Mostly by negative feedback
When excess of something causes the opposite to occur Excess CO2 causes increase in ventilation Hi B/P causes changes that lead to increase in B/P Positive feedback usually leads to vicious cycle and death (stimulus causes more of same) Acute blood loss of 2 L – not enough blood for heart to pump effectively, B/P falls, less blood to heart, lower B/P – continues until death |
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Useful positive feedback systems
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Clotting of blood leads to release of enzymes in area of injury which in turn act on unactivated enzymes in adjacent blood to cause more clotting
Uterine contractions get stronger in response to stretch of cervix – more stretch causes even stronger contractions Stimulation of nerve fibers propagates down length of fiber |
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Body is a social order of about ______ cells
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100 trillion
Organized into different functional structures (organs) Each functional structure contributes to maintenance of homeostatic conditions in ECF As long as internal environment maintained, cells live and function properly |
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Cell
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Basic living unit of body
Life sustained in each cell if surrounding fluid contains appropriate nutrients |
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Cell without organelles or nucleus
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Prokaryote
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Cell with organelles and well-defined nucleus
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Eukaryote
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Gel-like matrix within plasma membrane &
Contains organelles |
Cytoplasm
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Nucleus
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Control center of cell
Contains DNA which determine characteristics of cell |
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Protoplasm
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substances that make up cell
Composed of water, electrolytes, proteins, lipids, carbohydrates |
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principle compounds that make up living matter
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Carbon, hydrogen, oxygen, nitrogen
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most abundant substance in cell
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WATER
Makes up 70-85% of total cell mass (except fat cell) Body composed largely of H2O Helps transport substances between and within cell Important in heat regulation Body conserves H2O to conserve heat Dissipates excess body heat by releasing H2O via sweating What happens under general anesthesia? |
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Oxygen
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Necessary for maintenance of life
Enters body through aqueous lining of alveoli of lungs Transported to body cells via extracellular fluid How much by Hgb and how much dissolved? Participates in aerobic respiration within cell Needed for formation of adenosine triphospate (ATP) which provides energy for cell |
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Metabolic waste product of cellular metabolism
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CO2
Moves from cell into interstitial fluid then into plasma To lungs for removal from body CO2 levels maintained within narrow range for survival |
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Ions (electrolytes)
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Potassium, magnesium, phosphate, sulfate, bicarbonate, sodium, chloride, and calcium
Potassium and magnesium major intracellular ions Sodium and chloride principle extracellular ions |
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ion function
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Provide chemicals for intracellular enzyme reactions
Needed for cellular control mechanisms Maintain body fluid balance Cell membrane selectively keeps some in while keeping others out |
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Proteins
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Make up 10-20% of cell mass (second only to H2O)
Structural or globular proteins Structural Provide “cytoskeletons” of organelles Form intracellular filaments that provide contractile mechanism of all muscles Functional or globular Act as enzymes to accelerate chemical reactions in cell |
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Examples of Proteins
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Nucleoprotein
Protein plus nucleic acids Found in nucleus and participate in genetic control Lipoprotein Protein plus lipid Imbedded in cell membrane Glycoprotein Protein plus carbohydrate Act as receptors for hormones and neurotransmitters when on membrane surface |
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Lipids
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Generally insoluble in water
Soluble in fat solvents Cholesterol and phospholipids make up only about 2% of cell mass but BIG in function: Form cell membrane and intracellular membranes Stored in cell as triglycerides Make up to 95% of fat cell Storehouse of energy for cell that can be used as needed |
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Carbohydrates
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Average 1% of mass in most cells
3% in muscle cells 6% in liver Play major role in metabolism - provide much of the nutrient energy for cell processes Stored within cell as glycogen |
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Nucleic acids
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Large, complex molecules
Responsible for transmission of genetic information and control of cellular metabolism Two major types: DNA (deoxyribonucleic acid) RNA (ribonucleic acid) |
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Movement of cells
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Muscle cells generate forces that produce motion
Muscles attached to bone produce limb movement Contraction of smooth muscle cells in blood vessels change diameter of vessels Contraction of walls of bladder, urine empties |
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chief function of nerve cell
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Conductivity
Response to stimulus leads to electrical potential or wave of excitement that passes along surface of cell to reach its parts |
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Metabolic absorption
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all cells take in and use nutrients from their environment
Kidney tubules reabsorb fluids and synthesize proteins Intestinal cells reabsorb fluids and synthesize protein enzymes |
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Secretion
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Cells synthesize new substances from substances they absorb and secrete them to be used elsewhere
Adrenal gland, testes, ovaries secrete hormonal steroids |
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Excretion
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rid themselves of waste products
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Respiration
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All absorb O2 which is used to transform nutrients into energy (ATP)
Cellular respiration also known as oxidation |
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Reproduction
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Not all are capable of continuous division (nerve cells)
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Cell Communication
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Produces maintenance of dynamic steady state
Pancreatic cells secrete and release insulin to tell muscle cells to take up sugar from blood for energy |
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Cytoplasm
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Fluid contained in plasma membrane
Contains organelles and nucleus Cytosol Clear portion of cytoplasm Solution of water, ions, and organic molecules (glucose) |
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Largest membrane-bound organelle
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Nucleus
Contains large quantities of DNA Control center of cell Enclosed by 2 membranes – nuclear envelope Outer membrane continuous with endoplasmic reticulum membrane Nucleolus within nucleus contains large amounts of RNA and proteins Not all cells have nucleus (RBCs) Some have more than one (Skeletal muscle cells) |
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Functions of nucleus
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Cell division
Control of genetic information Replication of DNA – nucleus can make exact duplicate of genetic information in DNA for transmission to new cell Synthesis of RNA which is involved in synthesis of proteins and enzymes that direct cellular activity |
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Ribosomes
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RNA-protein complexes (nucleoproteins)
Synthesized in nucleolus & secreted into cytoplasm May float free in cytoplasm or attach to membrane of endoplasmic reticulum Function to provide sites for cellular protein synthesis |
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Endoplasmic reticulum (ER)
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Membrane factory”
Network of tubular or saclike channels Extends throughout cytoplasm and is continuous with outer nuclear membrane Total surface area (as in liver cells) can be 30-40 times cell membrane area Filled with fluid different from cytosol Synthesizes and transports protein and lipid components of most cell’s organelles Granular endoplasmic reticulum Rough from ribosomes attached to outer surface Agranular endoplasmic reticulum Smooth without ribosomes |
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Functions of ER
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Synthesis lipids, carbohydrates and enzymes
Involved in synthesis of steroid hormones in some endocrine cells Transports substances formed in some parts of cell to other areas Assists in drug elimination in liver cells Detoxifies harmful chemicals Ribosomes contain enzymes that detoxify substances that damage cells (such as drugs) by: Coagulation Oxidation Hydrolysis Conjugation with glucuronic acid Releases calcium into cytoplasm during contraction of skeletal muscle Plays role in development of malignant hyperthermia |
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Golgi apparatus
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Closely related to ER
Membranes similar to granular ER Usually composed of four or more stacked layers of thin, flat vesicles near one side of nucleus |
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What is Prominent in secretory cells where it’s located on side of cell that extrudes substances
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Golgi Apparatus
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Golgi Apparatus:
Functions |
Transported substances are processed in Golgi apparatus to form lysosomes, peroxisomes, secretory vesicles or other cytoplasmic components
Secretory vesicles break off from Golgi apparatus and migrate to intra- and extra-cellular destinations May fuse with cell membrane and release contents from cell (exocytosis) Neurotransmitters are released into the NMJ this way Endocytosis – cell membrane enfolds substance from outside cell, folds inward and separates from membrane forming vesicle that moves to inside of cell |
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Golgi Apparatus:
Functions (in association with ER) |
Packages” secretory products of cells
Transport vesicles (ER vesicles) continually pinch off from ER and fuse with Golgi apparatus Substances in ER vesicles transported from ER to Golgi apparatus |
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formed by breaking off from Golgi
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Lysosomes:
Scattered throughout cytoplasm Provide intracellular digestive system that allows cell to digest within itself damaged structures, food, unwanted matter (bacteria) Contain more than 40 digestive enzymes-hydrolases (hydrolytic enzymes) |
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Hydrolytic enzymes
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Hydrolytic enzymes split organic compound by combining H+ from H2O with one part of compound and hydroxyl (OH) part of H2O with other part of compound
Protein hydrolyzed to form amino acids Glycogen hydrolyzed to form glucose Lipids hydrolyzed to form fatty acids and glycerol |
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Lysosomes - pathology:
Discuss 2 disease |
Tay-Sachs disease
Leads to accumulation of a lipid (GM2 ganglioside) Absence of enzyme in lysosome See progressive destruction of nerve cells in brain and spinal cord Causes mental retardation, blindness, death 80% of time in persons of Jewish ancestry S/S by 3-6 months of age and death by 2-5 years – no treatment Gout Undigested uric acid accumulates in lysosome Lysosome membrane damaged Leaking of enzymes cause cellular death and tissue injury |
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Thought to be formed by budding off from smooth ER
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Peroxisomes:
Contains oxidases instead of hydrolases Oxidases combine H+ with O2 to form hydrogen peroxide (H2O2) H2O2 formed by many metabolic reactions Effective in oxidizing substances that would have toxic effect on cell Liver peroxisomes detoxify alcohol |
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“powerhouse” of cell
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Mitochondria:
Number varies depending on amount of energy needed by cell Without mitochondria, more than 95% of energy supply of cell would be eliminated and cellular death would occur Composed of two lipid bilayer-protein membranes Outer membrane is smooth and surrounds organelle Inner membrane is convoluted forming shelves with oxidative enzymes attached Matrix within contains large amounts of dissolved enzymes needed for extracting energy from nutrients |
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Oxidative enzymes within mitochondria essential to process of oxidative phosphorylation of carbohydrates, fats, and proteins that generates ____
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ATP
ATP is transported out of mitochondria diffusing through cell to release energy wherever needed Mitochondria self-replicate – divide whenever cell needs more ATP |
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Mitochondria pathology
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Cyanide blocks action of oxidative enzymes
Prevents use of O2 by cell See cyanide toxicity with nitroprusside when IV infusion rates exceed 8-10 mcg/kg/min (or when sulfur donors and methemoglobin are exhausted allowing cyanide radicals to accumulate) Acidosis early symptom – others: tachycardia, dyspnea, impaired mental status Expect when patient becomes resistant to Nipride |
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Treatment of cyanide toxicity
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Sodium thiosulfate 150 mg/kg IV over 15 minutes
Converts cyanide to thiocyanate If severe and patient unstable, give sodium nitrate 5 mg/kg slowly IV |
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Cell Membrane
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Thin membrane enclosing cell
Composed mostly of proteins (55%) and lipids (42%) and carbohydrates (3%) Basic structure Lipid bilayer only 2 molecules thick Large globular protein molecules interspersed in lipid bilayer Named lipid bilayer in 1935 In 1972, suggested that entire structure comprised a fluid “mosaic” capable of temporarily restructuring to allow entry of drugs and other substances into cell Current belief is that general and regional anesthetics work this way HOWEVER, actual mechanism by which anesthetics work is still unclear |
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Each lipid molecule is _______
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amphipathic
One part hydrophobic (uncharged, “water hating”) – repelled by water but mutually attracted to each other so line up in center of membrane where it’s protected from water One part hydrophillic (charged, “water loving”) – immersed in water |
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cell membrane Structure makes it cell impermeable to most _____-soluble molecules
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water, insoluble in oily inner core
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Phospholipid bilayer also contains cholesterol
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Makes the bilayer stronger, more flexible and more permeable
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cell membrane Serves as barrier to diffusion of water and hydrophilic substances but allows lipid-soluble molecules (O2 and CO2) to _____easily
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diffuse
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Cell Membrane Function
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Controls what goes in and out of cell
Communicates with other cells Receptors on the surface Connections between cells Desmosomes attach cells together like "glue“ Tight junction – outer cell membrane fuses Prevents passage of large molecules and H2O Gap junction – membrane doesn’t fuse Facilitates cell-to-cell passage of ions |
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Cell Membrane Proteins
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Usually glycoproteins (protein and carbohydrate)
May be integral proteins (protrude all the way through membrane) May be peripheral proteins that are attached only to one surface of membrane and don’t penetrate Receptor proteins Recognition proteins Transport proteins Channel proteins Carrier proteins |
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Integral proteins
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all the way through....
Provide channels for water molecules and water-soluble substances such as ions to diffuse through Allow preferential diffusion of some substances more than others May act as carrier proteins for transporting substances through membrane May act as enzymes |
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Peripheral proteins
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on surface...
Usually on inside of membrane Often attached to integral protein and function as enzyme or controller of intra-cellular function |
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Cell membrane carbohydrates
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Occur with protein or lipid as glycoprotein or glycolipid
Usually negatively charged Repel other negative objects Act as receptors for hormones such as insulin |
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Functions of membrane proteins and carbohydrates
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Maintain shape and structure of cell
Transport of substances across membrane Proteins are channel proteins or carrier proteins Responsible for “cell recognition” Cell surface recognition important in immune responses Transplanted tissue attacked by host because recognized as foreign tissue by immune system |
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What Plays major roll in controlling body fluid composition and Separates fluid of body into 2 compartments: Intracellular &
Extracellular |
cell membrane
There are Marked differences in compositions of two fluid compartments from Semipermeable nature of membrane Transport processes |
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Determinants of fluid composition in compartments
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Rate at which cells use and produce substances
O2 rapidly used by organelles removing it from intracellular fluid CO2 rapidly produced by cell causing intracellular concentration to be greater than extracellular Rate at which these substances enter and exit cell Membrane permeable to some substances & not others Dynamic structure capable of actively transporting substances through membrane |
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Passive transport
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Occurs naturally through any semipermeable barrier
Does not require energy Driven by diffusion hydrostatic pressure, osmosis Occurs by simple diffusion or facilitated diffusion Simple or passive diffusion Movement of solute from area of greater concentration to area of lesser concentration along concentration gradient Kinetic movement of molecules through spaces without binding to carrier protein |
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Simple or passive diffusion occurs by 2 pathways
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Lipid soluble molecules diffuse thru lipid bilayer
Molecules thru watery channels that are all the way thru transport proteins |
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Facilitated diffusion (passive mediated transport)
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Molecule transported without energy but requires carrier protein to move through membrane
Glucose transported by facilitated diffusion |
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Diffusion rate depends on
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How great the concentration gradient
Differences in electrical potential across membrane Pores in lipid bilayer often linked with Ca++ so other cations diffuse slowly because they’re repelled by + charge Size of molecule – Graham’s Law of Diffusion Rate of diffusion of a gas will vary with the square root of its molecular weight Gas with MW of 4 (sq. root = 2) will diffuse twice as quickly as gas with MW of 16 (sq. root = 4) Lipid solubility – diffusion coefficient directly related to solubility in lipid of most substances One of the most important factors that determine rate of diffusion Drugs that are more lipid soluble have a more rapid onset of action Onset of action is related to lipid solubility Temperature – the higher the temperature, the faster particles move about so the faster the rate of diffusion Distance a substance must diffuse – the shorter the distance, the faster the rate |
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Another factor influencing passive transport is hydrostatic pressure
...define it. |
Defined as the mechanical force of water pushing against cell membranes
In vascular system = B/P Blood reaching capillary bed has hydrostatic pressure of 25-30 mm Hg Sufficient to push water across capillary membrane into interstitial space (filtration) |
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Osmosis
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net diffusion of water.....
Movement of water “down” concentration gradient Movement across semipermeable membrane from region of higher water concentration to lower water concentration Related to hydrostatic pressure and solute concentration but not particle size or weight Osmolality – # of milliosmoles per kg (weight) of water (one osmole is 1 gram of undissolved solute) |
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Osmolarity
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# of milliosmoles per liter (volume) of water
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Normal osmolality
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Normal osmolality of body fluids is 280-294 mOsm/kg
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Body attempts to equalize osmolality of intra- and extracellular fluids to maintain _____status
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hydration
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Osmotic pressure
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Osmosis moves a solvent in one direction only
From a less concentrated solution to a more concentrated solution As osmosis proceeds, pressure builds up on the side of the membrane where volume has increased Ultimately pressure prevents more water from entering and osmosis stop Osmotic pressure of solution is pressure needed to prevent or stop osmosis Amount of pressure required to oppose osmotic movement of water Counter to hydrostatic pressure Determined by type and thickness of membrane, size of molecules, concentration gradient and solubility of molecules within membrane Water is moved in glomerulus in kidney and capillaries of microcirculation due to hydrostatic and osmotic forces |
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Substances may diffuse directly through ____channels in protein
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open
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Selective permeability
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channels highly selective to specific ions....
Determined by characteristics of channel itself Diameter, shape, electrical charge along inner surface Positively charged channel repels positively charged ions Na+ channels allow only Na+ to pass, Ca++ only Ca++, etc. |
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Unequal distribution of charges between extra-cellular and intra-cellular effects rate of _____
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diffusion.....
Difference in charge known as resting membrane potential Most cells negatively charged on inside in relation to extra-cellular fluid Concentration and charge difference influence direction and rate of ion diffusion between ICF and ECF compartments – electrochemical gradient |
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Gating of protein channels
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Believed that gates are actual gate-like extensions of protein molecule
Can close over opening of channel or open by conformational change in shape of protein Voltage gating – conformation of gate directed by electrical potential across cell membrane Ligand gating – conformational change occurs when ligand (chemical substance) binds with protein |
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Active transport
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when molecules are pulled “uphill” against concentration, electrical or pressure gradient
Requires energy from ATP Depends on carrier proteins that penetrate through membrane |
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Na+-K+-ATPase pump (Na+-K+ pump)
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In membranes of all cells
Pumps Na+ from ICF to ECF and K+ from ECF to ICF (Na+ out and K+ in) Each ion moves against its electrochemical gradient Carrier protein has 3 receptor sites for binding Na+ on inside of cell Carrier has 2 receptor sites for binding K+ on outside |
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When K+ bound to outside and Na+ bound to inside, ATPase becomes _____
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activated
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ATPase
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enzyme that provides enough energy to transport Na+ ions against concentration gradient as great as 20 to 1 and K+ ions against gradient as great as 30 to 1
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Energy from ATP causes conformational change in protein and ___ Na+ ions are extruded to outside of cell and ___K+ ions to inside
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3, 2
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Na+- K+ pump Functions
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Functions to control volume of cell
Pumps Na+ out so cell won’t burst from osmosis of water into cell 3 Na+ out for every 2 K+ in – net loss of ions which initiates osmosis of water out of cell Creates electrical potential across membrane – important in transmission of nerve and muscle signals Helps maintain electrochemical gradient necessary for resting potential Cardiac glycosides (digitalis) inhibit this pump causing increase in intracellular Na+ and decrease in K+ (↑ Na+ levels ↓ extrusion of Ca++ → ↑ contraction) |
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Ca++ATPase pump
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present in sarcoplasmic reticulum (ER of muscle cells)
Sarcoplasmic reticulum (SR) contains Ca++ ions in very high amounts Ca++ATPase pump responsible for maintaining low intracellular Ca++ concentration MH results from rapid increase and very high Ca++ level in skeletal muscle throughout body |
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H+-K+ ATPase pump
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In gastric parietal cells
Pumps H+ from ICF of parietal cells into stomach where it acidifies gastric contents Omeprazole (Prilosec) inhibits this pump |
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Resting membrane potential
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Difference in charge inside and outside cell when cell is in “polarized” or resting state
Normally negative Inside slightly more negative than outside Ranges from -10 mV in RBCs to -90 mV in heart and skeletal muscles (-50 to -90 nerve cells) Difference in voltage across membrane due to differences in ionic composition of ICF and ECF |
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Action potential
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Rapid change in membrane potential that results when cell receives stimuli that exceeds membrane threshold
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Threshold potential
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Point at which cell will continue to depolarize with no further stimulation
Usually after depolarized by 15-20 mV Action potential becomes inevitable |
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Depolarization
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Membrane potential becomes less negative (moves toward zero) so cell is more positively charged and polarity is neutralized
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Hyperpolarization
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Process of making membrane potential more negative (than resting membrane potential)
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Inward current
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Flow of positive charge into cell
Depolarizes membrane potential |
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Outward current
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Flow of positive charge out of cell
Hyperpolarizes membrane potential |
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Overshoot
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Portion of action potential when membrane potential is positive
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Undershoot
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Portion of action potential following repolarization when membrane potential more negative that at rest
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Refractory period
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Period during which another normal action potential cannot be elicited in excitable cell
May be absolute Time when no matter what the strength of stimulus, action potential cannot be elicited May be refractory Time when stronger than normal stimuli can cause action potential |
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At rest, membrane potential inside cell is ___ to ____ mV (depending on type) more negative than the potential in ECF on outside – cell is “polarized”
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-70 to -90
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Resting Membrane Potential Established & maintained by ??
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Diffusion of K+ out of cell through K+ leak channels – permeability to K+ is high
Diffusion of Na+ in through Na+ leak channels – permeability to Na+ is low Contribution of the Na+-K+ pump (2 K+ in and 3 Na+ out) |
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When does action potential begin?
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Begins with sudden change from normal resting negative membrane potential to positive potential and ends with rapid return to negative potential
Will not occur until initial rise in membrane potential is great enough to reach threshold Once threshold reached rapid spread of action potential occurs |
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Propagation
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Action potential elicited at any one point on excitable membrane usually excites adjacent membrane with spread of potential over entire membrane
Travels in all directions away from stimuli Once it starts, continues over entire membrane if conditions are right or may not travel at all if conditions are not right – “all or nothing” |
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Concerning Thresholds: Number of Na+ ions entering _____number of K+ leaving
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exceeds
Some cells exhibit automaticity (cardiac cells) Threshold is reached without outside stimuli Leak of Na+ channels causes pacemaker cells to reach threshold with spontaneous action potential Sudden rise in membrane potential to threshold causes explosive development of action potential and depolarization of membrane |
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Concerning Depolarization: Membrane becomes very permeable to ____ ions
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Na+
Large numbers of positively charged ions enter cell Normal “polarized” state of – 90mV is neutralized as potential rises in positive direction Known as depolarization May see overshoot with potential exceeding zero Within 10,000ths of a second, Na+ channels begin to close and K+ channels open Diffusion of K+ out re-establishes normal resting potential - repolarized |
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Voltage-gated Na+ and K+ Channels
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Na+ and K+ ions move in and out of the cell via Na+-K+ pump, Na+-K+ leak channels, and voltage gated Na+ and K+ channels
Voltage-gated Na+ channels have activation and inactivation gates When threshold is reached, conformational change in activation gate of Na+ channel causes it to open and Na+ ions pour in Increase in action potential that opens activation gate also causes change that closes inactivation gate – but slower process Net result is rapid influx of Na+ for split second K+ channel closed during resting state Action potential causes slow conformational opening of gate and allows increased diffusion of K+ out Slow compared to Na+ channels Open at same time Na+ channels are closing Decrease in Na+ in and increase in K+ out speeds repolarization process |
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Activation gates in Na+ channels ____rapidly
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OPEN...
Influx of Na+ causes membrane potential to become even more positive and depolarization occurs Locals block these voltage-sensitive Na+ channels and prevent occurrence of nerve action potentials |
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REpolarization results in _____ __ _____ _______
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closure of Na+ channels
Inactivation gates on Na+ channels respond to depolarization by closing but more slowly than opening of activation gates |
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Depolarization opens K+ channels but ____
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SLOWLY
Opening at same time Na+ channels are starting to close (inactivation gates) |
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Refractory Period
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Excitable cells incapable of producing normal action potential
Absolute Cannot respond to additional stimuli Relative During late phase, permeability to K+ increases and stronger than normal stimulus can evoke action potential |
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Electrical synapses
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Allow current to flow from one excitable cell to next via low resistance pathways between cells
Called gap junctions Found in cardiac muscle and some types of smooth muscle Account for the very fast conduction in these tissues Cell-to-cell conduction in cardiac ventricular muscle, uterus, and bladder allow these tissues to be activated simultaneously for coordinated contraction |
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Chemical synapses
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Synaptic cleft – gap between pre and post synaptic cell membrane
Information is transmitted across synaptic cleft via neurotransmitter A substance that is released from presynaptic terminal binds to receptors on postsynaptic terminal |
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Synaptic and Neuromuscular Transmission
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Sequence of events within chemical synapse
Action potential in presynaptic cell causes Ca++ channels to open Influx of Ca++ into presynaptic terminal causes neurotransmitter, which is stored in synaptic vesicles, to be released by exocytosis Neurotransmitter diffuses across synaptic cleft and binds to postsynaptic membrane Produces change in membrane potential on post synaptic cell |
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Change in membrane potential on postsynaptic cell membrane can be excitatory or inhibitory depending on neurotransmitter released
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If excitatory, causes depolarization of postsynaptic cell
If inhibitory, causes hyperpolarization of postsynaptic cell (becomes even more negative so takes greater stimulus to reach threshold |
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Neuromuscular Junction
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Example of chemical synapse
Nerves that innervate muscle fibers are motor neurons A single motor neuron and the muscle fibers it innervates is a motor unit Motor units can range from a few muscle fibers to thousands of muscle fibers Small motor units involved in fine motor activities Large motor units involved in gross muscular activities |
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Sequence of Events at NMJ
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Synapse between motor neuron and muscle fiber is neuromuscular junction
Action potential between motor neurons produce action potential in muscle fibers it innervates Action potential propagated down motor neuron Local currents depolarize each adjacent region to threshold Presynaptic terminal is depolarized causing voltage-gated Ca++ channels in presynaptic membrane to open Ca++ flows into terminal causing storage vesicles of neurotransmitter, acetylcholine (ACh) to fuse with terminal membrane and release ACh from synaptic vesicles by exocytoses ACh diffuses across synaptic cleft to postsynaptic membrane (motor end plate) ACh binds to 2 of 5 subunits (2 alpha subunits) of nicotinic cholinergic receptor on motor end plate When both alpha receptors on motor end plate are occupied by ACh, a conformational change in the ion channel in core of the receptor opens and cations flow through channel – Na+ and Ca++ in and K+ out Propagation of action potential spreads over surface of skeletal muscle fibers leading to contraction Acetylcholinesterase Enzyme embedded in motor end plate membrane near ACh receptors causes rapid hydrolysis of ACh Ion channels close, end plate repolarizes Na+ channels in muscle membrane also close, reuptake of Ca++ occurs into SR and muscle cell relaxes |
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Acetylcholinesterase
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Enzyme embedded in motor end plate membrane near ACh receptors causes rapid hydrolysis of ACh
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Muscle Relaxants and the NMJ
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Non-depolarizing muscle relaxants compete with ACh for nicotinic receptors on motor end plate (act as antagonists at receptor)
Do not cause change in receptor 70% of receptors blocked do not cause evidence of block Neuromuscular transmission fails when 80-90% of receptors occupied Depolarizing muscle relaxants (succinylcholine) resemble ACh and cause generation of action potential when it binds with alpha subunits on ACh receptor (acts as agonist at receptor) Causes conformational change as does ACh Succinylcholine is not metabolized by acetylcholinesterase in NMJ so see longer effects from more prolonged depolarization of motor end plate than with ACh |
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Anticholinesterases
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(Neostigmine)Prevent degradation of ACh in synaptic cleft and prolong and enhance action of ACh at motor end plate (more is available)
Used to reverse neuromuscular blocking drugs Also used to treat myasthenia gravis Occurs in about 1 in 20,000 people Inability of NMJ to transmit signals from nerve fibers to muscle fibers causes paralysis |
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Myasthenia gravis
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Believed to be autoimmune disease in which patients develop antibodies against their own ACh receptors
See decreased # of receptors Decreased transmission of nerve impulses Incomplete or no muscle depolarization Treated with anticholinesterases which allow more ACh to accumulate in synaptic cleft |
