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73 Cards in this Set

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Flux equation (Fick's law for movement of a solute through solution).

or, Jx=Px(Xo-Xi)

or, Jx=Px(Xo-Xi)

Px

permeability coefficient, combines lipid/ water partition coefficient, diffusion coefficient, membrane thickness, and a standard 1-micron squared area.




specific for a given molecule/ ion and largely affected by the number and types of channels that the ion can pass through.

Gated channels

opened/closed by chemical, voltage, mechanical, or other forces.

Non-Gated Channels

pores, passive channels, leaky channels.

Leaky Channels

Ion-Specific




important in determining the resting properties of the cell.




Include membrane resistance and resting membrane potential.

Jmax

maximum flux. at this point, movement of ions through channels may not follow fick's law (which says the increase in concentration gradient leads to a linear increase in flux).




due to limited number of channels for ion to move through.




Never happens physiologically.

Ohm's Law

V=IR

Conductance (G)

G=1/R



Current

I=GV


I=V/R

Permeability vs. Conductance

Permeability: ability of an ion to move across membrane. Dependent on number of channels.




Conductance: actual electrical measurement of the movement of ions. Directly related to flux.

Current units

nanoampere (nA)


picoampere (oA)

Conductance units

picosiemens


nanosiemens

electrochemical equilibrium

electrical force equals the diffusion force so no net change in concentration.

Nernst Equation

Tells us voltage at which an ion is in electrochemical equilibrium, given initial conditions.

Tells us voltage at which an ion is in electrochemical equilibrium, given initial conditions.





Resting membrane potential

Potential due to all the ions electrochemical equilibriums.




Sum of currents must equal 0.




Ik+INa = 0




Ik=-INa

Goldman-Hodgkin-Katz equation

measure resting potential of cells (multiple ions)

P is permeability of that ion.

measure resting potential of cells (multiple ions)




P is permeability of that ion.

Permeability

dependent on number of ion channels for that specific ion.

Equilibrium vs. Resting Membrane Potential

Equilibrium: does NOT require energy to reach. given ion simply flowing in and out at equal rate.




Resting membrane potential: steady state. requires energy, usually in form of ATPase pump. ion not in equilibrium.

Conductance Equation for I, current

I = G (Vm -Eeq)




Use this to calculate the current of a specific ion through a membrane.




(Vm-Eeq) is the driving force for ion movement.




If resting membrane potential is equal to the equilibrium voltage for a given ion, that ion will not have a net current.

reversal potential

If resting membrane potential is equal to the equilibrium voltage for a given ion, that ion will not have a net current.

Resting membrane potential at steady state


Types of channels include

-Voltage gated


-Ligand gated


-Pressure/stretch gated


-Non-gated (passive leak)


-Water channel (aquaporins)

structure of Ion Channels

derived from primary AA sequence.


multiple subunits, each with distinct transmembrane segments (domains) that fulfill distinct roles.




Each subunit in VG channel consists of 6 transmembrane helices.

Electrical Circuit Model for membrane



threshold

voltage at which a depolarization can trigger an action potential.

depolarization

to make voltage less negative

hyperpolarization

to make voltage more negative

decreasing potential.

refers to absolute value, meaning making less negative.

tetrodotoxin (TTX)

toxin that blocks the sodium gated ion channels and will cause respiratory failure quickly.




effects irreversible.

voltage clamp experiments

membrane voltage is artificially held static at certain voltage and current is observed.




Because I=GV, and V held constant, measuring conductances, which are related to number of certain channels on membrane (permeability).

depolarization phase caused by

opening of voltage gated Na+ channels, allowing Na+ to rush into cell, making membrane potential less negative to a positive maximum called overshoot.

Depolarization starts when

Na+ channels inactivate and delayed rectifier voltage gated K+ channels open.

undershoot

slight hyper polarization at the end of the AP. due to long lasting activation of the K+ channels after depolarization.

excitable cells

include cells that display APs, heart, muscle, nerve. typically have lots of Na+ channels. voltage at the peak of the AP is closest to equilibrium potential of Na+, ENa.

voltage clamp technique

allows one to hold membrane voltage at a fixed value, even when conductance is changing to measure the current.




Because voltage cannot change, any change in current is direct result of change in conductance.

inward negative

positive ions flow into cell making negative currents draw downward. sodium entering the cell.

TTX (Tetrodotoxin)


STX (Saxitoxin)

TTX-produced by puffer fish.


STX- produced by algae responsible for red tide.




both are specific sodium channel blockers.

TEA (tetraethyl ammonium)

selectively blocks outward flow of potassium.

current clamp

holding current constant and measuring voltage.




sticking an electrode in a cell and measuring changing membrane potentials during AP is done with current clamp.

patch clamp

variant of voltage clamp. allows us to voltage clamp a tiny piece of membrane "patch" to study the current produced by a single channel activity.




patch can be attached to cell or excised.

Sodium channels

-fast acting.


-exhibit inactivation.


-3 conformations: open, closed-inactivated, closed- essential for AP to travel down axon.




stimulus given, channel senses this and opens. opening increases conductance, increase in current. just after peak, the channel closes and enters closed-inactivated (depends on both time and voltage). channel remains inactive until cell repolarizes and enters closed confirmation.







closed-inactivated

Na-channel conformation that's dependent on both time and voltage.


During this conformation, another spike cannot happen.

closed state

Na-channel conformation. another AP can be initiated, but requires stronger depolarizing stimulus.

K channels vs. Na channels

-K channels open slower than sodium channels.


-do not exhibit inactivation-remain open as long as cell is depolarized.

Action Potential sequence of events

-Membrane depolarization opens VG sodium channels.

-sodium rushes into cell.


-cell depolarizes, opening more sodium channels.


-membrane potential driven up to Erev > Na channels inactivate (cause decrease in GNa) and deploy opens VG K channels to increase GK.


-K rushes out to depolarize cell.


-Local circuit currents produced which allow propagation to near by membrane.

Action Potential

self-sustaining, regenerative current driven by influx of sodium and efflux of potassium.

absolute refractory period

another AP cannot occur because Na channel is closed-inactive.

relative refractory period

due to persistent activation of K channels which keep the cell hyper polarized longer than it would normally be. another AP can occur, but stimulus must be stronger.

threshold

voltage at which an AP can start. one cannot define threshold for single channel current.

extracell Ca2+ effects on VG Na channels

-Ca2+ changes the way the VG Na channel senses changes in membrane potential because charge shielding effects on voltage sensor.




-higher than normal extracell Ca2+ > decreased excitability




-lower than normal extracell Ca2+ > hyper excitability.



Big drop in Ca2+ may lead to

-tetany of peripheral nerves


-paralysis of respiratory muscles.

space constant

how far an AP can passively travel due to decrement in voltage before it reaches 37% of initial strength.  

Rm=membrane resistance
Ri=internal resistance given as inverse of the dam of cell.

how far an AP can passively travel due to decrement in voltage before it reaches 37% of initial strength.




Rm=membrane resistance


Ri=internal resistance given as inverse of the dam of cell.

increase space constant..

increase space constant, increase the speed and distance an AP will travel.




you can increase the constant by:


-increasing axon diameter, thereby dec internal resistance.


-increasing membrane resistance, so reducing amt of current lost.



What affects membrane resistance?

-properties of phospholipids


-number of leak channels


-presence of myelin

capacitance

-inherent property of membrane.


-membrane acts as capacitor by separating and storing the intra and extracellular charge.


-in case of current clamp, response to injected current will be slowed by capacitance.


-voltage clamp-no effect of capacitance.

time constant

amount of time required to charge and discharge the membrane capacitance.




time constant=Rm x Cm (membrane resistance x membrane capacitance)





Action potentials and capacitance

-During action potential, flow of ions charge membrane and so the action potential becomes weaker.




-if we could decrease capacitance, we could speed the signal propagation.

Myelination

-decrease time constant and increase space constant.




-oligodendrocytes in CNS and Schwann cells in the PNS wrap axons with myelin, thereby decreasing membrane capacitance and increasing resistance. successive layers of myelin thicken membrane and increase distance b/w places of capacitor.




-Thus, increases Rm and decreases Cm.


-reduction in CM outweighs increase in RM, having an overall effect of reducing the time constant and increasing conduction velocity.

Nodes of Ranvier

-points along axon in which the myelin is absent.


-contain concentrated grouping of the voltage gated Na and K channels that are absent in the myelinated sections.


-nodes create saltatory conduction. (AP jumps from node to node by getting boost at each node).

eukaryotic membranes contain

1) phospholipid bilayer matrix (hydrophobic interior)


2) intrinsic membrane proteins (can be extracell or intracell, cannot be removed w/o destroying membrane).


3) extrinsic membrane proteins (only extracell, can be removed w/o disrupting membrane integrity).


4) glycolipids, glycoproteins, and cholesterol.

Membrane Fxns

-serves as reactive surface


-compartmentalizes the cell


-controls entry and exit of molecules.

Px, permeability coefficient

from Fick's Law, Jx=Px(Xo-Xi)




Px made up of 4 components:


-Lipid/Water Partition Coefficient (B)-ratio of molecule's solubility in oil to its solubility in water. (0=soluble in water, 1=soluble in lipid, more flux)


-Diffusion Coefficient (Dx)-increasing Dx will increase Jx.


-Membrane thickness (X)-assumed constant for most membranes.


-Area considered. typically 1 sq/micron.

Pore (non-gated channel)

also called leakage channels.


number and type of pore channels responsible for the resting membrane potential.

Channel (gated-pore)

channels are conduits gated by a door, and responsible for all other potentials on a membrane such as action potentials and synaptic potentials.




open in response to sound, light, mechanical stretch, voltage or chemicals.

3 examples of gated channels

1) Voltage-gated sodium channels.


2) Gap Junction Channel


3) Ligand-gated Channel

Voltage-gated sodium channels

-opens in response to voltage change in membrane.




-multimeric protein and forms an ion channel, selecting for sodium.



Gap Junction Channel

-formed when two hemichannels from adjacent cells simultaneously open and ions pass b/w adjacent cells.



Ligand-gated channel

Binding of ligand (acetylcholine, for example) to its receptor causes channel to open and allow sodium and potassium to move through channel.

Components of a typical ion channel

1. Gate


2. Ion Selectivity Filter


3. Typically they are glycoproteins


4. Have anchor proteins to keep them stabilized to lipid bilayer.


5. Voltage sensors or ligand binding site.

Ion channel structure

-multiple-pass transmembrane domain-containing chains of AAs.


-some have alternating b/w hydrophobic and hydrophilic AAs, telling you it spans membrane multiple times.


-N terminal inside membrane.


-P-loop referred to as pore domain-loose binding of ions.

Tetramers

-voltage gated Na+


-voltage gated Ca2+


-voltage gated K+



Pentamers

-Nicotinic ACh receptor channel (ligand-gated channel in synapse).

Hexamers

-Connexon- 6 unit structure that makes up half an entire gap junction channel.


-A connexon in a cell's membrane aligns with adjacent cell's connexon hexameter to propagate electrical potential.