Resting Membrane Potential

Membrane potential at which neuron membrane is at rest, ie does not fire action potential Written as Vr

Ionic Equilibrium Potential

Membrane Potential (potential difference across the plasma membrane) at which the net flow of an ion type = zero The number of ions moving into the cell = the number of ions moving out of the cell for a particular species of ion

Nernst Equation Variables

Assumes that membrane is permeable to that ion As temperature increases the diffusion increases As charge on the molecule increases, it decreases the potential differences needed to balance diffusion forces.

Simplified Eion (at 37C)

Eion = 2.303 RT/zF log [ion]o/[ion]in

Ena = 61.54mV log [Na]o/[Na]I = 62 mV

EK = 61.54mV log [K]o/[K]I = -80 mV ECa = 30.77mV log [Ca]o/[Ca]I = 123 mV CCl = -61.54mV log [Cl]o/[Cl]I = - 65 mV

Goldman Equation
Vr= RT/F ln Pk[K]o+Pna[Na]o+PCl[Cl]i Pk[K]I+Pna[Na]I+PCl[Cl]o Also known as the constant field equation because it assumes that electrical field of the membrane potential is equal across the span of the membrane

Membrane Permeability
Membrane is 50 more permeable to K than to Na Pk/Pna = 50 PCl/Pk = 0 The membrane is so impermeable to Chloride that you drop it from the equation

Goldman Equation
Vr= RT/F ln Pk[K]o+ Pna[Na]o+ PCl[Cl]i Pk[K]I+ Pna[Na]I+ PCl[Cl]o Eion = 2.303 RT/zF log Pk[K]o+Pna[Na]o Pk[K]I+Pna[Na]I Vr= 61.54 mV log 50[5]o +1[150]o 50[100]i+1[15]I = - 65mV

Not to study
Donnans equilibrium Osmolarity considerations

Action Potential
Changes in Ion Permeability allows inward Na flux and triggers an increased outward K flux through voltage gated ion channels Causes transient change in Membrane Potential The change in ion permeability is triggered by transient depolarization of the membrane

Conductance = g
How many charges (ions) enters or leaves cell (inverse of resistance) due to:
number of channels/membrane area
Highest density at axon hillock

number of open channels ion concentration on either side of membrane Measured in Siemens (S), in cells pS (pico; -12)

Historical Figures
Hodgkin and Huxley won Nobel Prize for Voltage clamp in 1961 used to identify the ion species that flowed during action potential Clamped Vm at 0mv to remove electric driving force than varied external ion concentration and observed ion efflux during a voltage step Sakman and Nehr won Nobel Prize for Patch Clamp in 1991 measured ion flow through individual channels shows that each channel is either in open or closed configuration with no intermediate. The sum of many recordings gives you the shape of sodium conductance.

Information Coding
Is NOT in shape of action potential Is in the action potential frequency of firing how many are triggered In the action potentials pattern or timing of propagation

Conductance = g
How many charges (ions) enters or leaves cell (inverse of resistance) due to:
number of channels/membrane area
Highest density at axon hillock

number of open channels ion concentration on either side of membrane Measured in Siemens (S), in cells pS (pico; -12)

Generation of Resting Membrane Potential (-70mV)

Plasma membrane Selective permeability, permeable to K, not Na Unequal distribution of ions across membrane
Due to open potassium channels and closed sodium and chloride channels

Action of ion pumps 3Na/2K ATPase

Ion
K+ NA+ ClH2O Anion-

Inside
125 12 5 55,000 108

Outside Cross PM
5 120 125 55,000 0 yes no yes yes no

Ionic Equilibrium Potential

The membrane potential that balances the ions concentration gradient so that there is no net current for that ion.
No permeability factor.

Equilibrium Potential of An Ion

The membrane potential at which the net driving force propelling the ion in = the net driving force propelling the ion out. Written Eion; ENa, ECl, EK

Nernst Equation
Eion = 2.303 RT/zF log [ion]o/[ion]in
Eion = ionic equilibrium potential Z= charge of ion F= Faradays constant T= absolute temperature (0Kelvin/-273C) R= gas constant

Action Potential: a transient and rapid sequence of changes in the membrane potential Action Potentials Can travel up to 100 meters/second Usually 10-20 m/s 0.1sec delay between muscle and sensory neuron action potential

Membrane Permeability
Membrane is 50 more permeable to K than to Na Pk/Pna = 50 PCl/Pk = 0 The membrane is so impermeable to Chloride that you drop it from the equation

Goldman Equation
Vr= RT/F ln Pk[K]o+ Pna[Na]o+ PCl[Cl]i Pk[K]I+ Pna[Na]I+ PCl[Cl]o Eion = 2.303 RT/zF log Pk[K]o+Pna[Na]o Pk[K]I+Pna[Na]I Vr= 61.54 mV log 50[5]o +1[150]o 50[100]i+1[15]I = - 65mV

Ion Permeability
Changes during action potential The plasma membrane becomes permeable to sodium ions
Permeability increases from 0.02 to 20=1000 fold increase

Causes Em aka Vr to approach Ena at positive voltages = +20mV

overshoot

Falling rising

undershoot

6 Characteristics of an Action Potential

#1 Triggered by depolarization

a less negative membrane potential that occurs transiently

Understand depolarization, repolarization and hyperpolarization

#2 Threshold
Threshold depolarization needed to trigger the action potential
10-20 mV depolarization must occur to trigger action potential

#3 All or None
Are all-or- none event Amplitude of AP is the same regardless of whether the depolarizing event was weak (+20mV) or strong (+40mV).

#4 No Change in Size
Propagates without decrement along axon
The shape (amplitude & time) of the action potential does not change as it travels along the axon

#5 Reverses Polarity
At peak of action potential the membrane potential reverses polarity Becomes positive inside as predicted by the Ena Called OVERSHOOT
Return to membrane potential to a more negative potential than at rest Called UNDERSHOOT

#6 Refractory Period
Absolute refractory period follows an action potential. Lasts 1 msec
During this time another action potential CANNOT be fired even if there is a transient depolarization. Limits firing rate to 1000AP/sec

Stimulating electrode: Introduces current that can depolarize or hyper-polarize

Recording electrode: Records change in Potential of the membrane At a distance away

At Threshold Na influx equals K efflux

Voltage (mVolts) along Y axis

Time (msec)

Voltage Sensitive Ion Channels

Sodium Potassium

Ionic Equilibrium Potential

Membrane Potential (potential difference across the plasma membrane) at which the net flow of an ion type = zero The number of ions moving into the cell = the number of ions moving out of the cell for a particular species of ion

Regenerative Process: Once one Na channel Opens, Na enters, Depolarizes membrane, More and more Na Channels open leading to More sodium influx & causes upward & depolarizing (more +) phase of the AP

What does a sodium Channel look like? It is one large protein With 4 domains that Each loop through the Plasma membrane 7 Times.

Property of Voltage Dependent Sodium Channel

Sodium channel opens for 1-2 millisecond following threshold depolarization then inactivates and does not open even if Vm is depolarized. This is called sodium channel inactivation and contributes to the repolarization of Vm

Na Channel Gates
M gate= activation gate on Na channel; opens quickly when membrane is depolarized H gate- inactivation gate on Na channel; Closes slowly after membrane is depolarized causes the absolute refractory period for AP propagation

Potassium Channel Property

K channels open with a delay and stay open for length of depolarization Repolarize the Vm to Ek= -75mV which is why you have hyperpolarization.
Also called a delayed rectifier channel

Gate on the Delayed Rectifier Potassium Channel K channels have a single gate (n) that stays open as long as Vm is depolarized. n gate on K channels opens very slowly this allows the Vm to depolarize due to Na influx; Na and K currents do not offset each other right away

Refractory Period
Refractory period due to Na channel inactivation and the high gk Subsequent Action potential cannot be generated

2 ways to increase AP propagation speed

Increase internal diameter of axon which decreases the internal resistance to ion flow Increase the resistance of the plasma membrane to charge flow by insulating it with myelin.

See and understand what happens to the form Of the action potential When you add a voltage Sensitive calcium channel And a calcium gated Potassium channel Test question : think about This and the next 2 slides

Channel Density
Density is how many channels are in a unit area of plasma membrane, ie how closely they are packed together. Determines the length of the membrane that will be depolarized at a given time

Understand
Regenerative nature of action potential Orthodromic and antidromic Voltage gates in sodium channel Threshold potential sodium and potassium fluxes are balanced Initial segment of axon = axon hillock Two mechanisms for increasing speed of action potential propagation Saltatory conduction

Understand
Action potential occurs because sodium and potassium fluxes change the charge on the cell membrane not because the fluxes change ion concentrations.

Definition
V=IR
g=1/R

V=voltage, I=current, R=resistance

g=conductance

Vm=membrane voltage

Vr=voltage of membrane at rest

Permeability and Conductance

gna is low at Vr because sodium channels are closed
gk is higher than gna at Vr because some potassium channels are open. V=I/R Ohms Law G=conductance=1/R

Definitions
Current=net flow of ions per unit time 1 ampere of current represents movement of 1 coulomb of charge per second Resistance- frictional forces that resists movement of ions or charges Measured in ohm
Current (A)= V/R

Definitions
Capacitance refers to the Conductance is the ability of plasma reciprocal of membrane to store or resistance and separate charges of opposite signs. measures the ease with which current flows in Myelin has high capacitance so stores an object. charges and ions do not move across the Measured in siemens membrane (S)
Measured in Farads