resting membrane potential 1 mv= 0.001 v membrane separates intra- and extracellular compartments...

Resting membrane potential

•1 mV= 0.001 V

•membrane separates intra- and extracellular compartments

•inside negative (-80 to -60 mV)

•due to the asymmetrical distribution of ionsacross the cell membraneAND the differential permeability of the membrane to these ions

Channels allow ions to diffuse across membranes

Voltage-gated: Na+ channels, K+ channels, Ca2+ channelsLigand-gated: neurotransmitters (acetylcholine, glutamate)

Figure 5-34a

Potassium Equilibrium Potential

Figure 5-34b

Figure 5-34c

Resting membrane potential is due mostly

to high potassium permeability

The Nernst equation describes an ion’s equilibrium potential

Eion RT

zF ln

[ion]out

[ion]in

where:R is the gas constant (8.314 X 107 dyne-cm/mole degree), T is the absolute temperature in o Kelvin, z is the charge on the ionF is the Faraday (the amount of electricity required to chemically alter one gram equivalent weight of reacting material = 96,500 coulombs).

A simpler version of the Nernst equation

At 37ºC:

When ions can move across a membrane, they will bring the membrane potential to their equilibrium potential.

Eion 61

z log

[ion]out

[ion]in

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Typical ion concentrations

Calculating the membrane potential for a cell that is only permeable to K+

[K+]out = 5 mM[K+]in = 150 mM

Ek = 61 x (-1.5) = -92 mV

Eion 61

z log

[ion]out

[ion]in

EK 61

1 log

[5]

[150]

Sodium Equilibrium Potential

ENa = 61 x 1 = +61 mV

ENa 61

1 log

[150]

[15]

The Na+-K+-ATPase (“sodium pump”) works to keep intracellular K+ high and Na+ low

• The membrane potential can be described by the relationship between ion permeabilities and their concentrations

• The Goldman equation:

• Vm =

PNa[Na+]out+ PK[K+]out+ PCl[Cl-]in

Predicting the membrane potential (Vm)

PNa[Na+]in+ PK[K+]in+ PCl[Cl-]out

61 log

At the resting potentiala. K+ is very close to equilibrium.b. Na+ is very far from its equilibrium.c. PK >> PNa

Real neurons and “Dynamic Polarization”

Pyramidal cellLayer V neocortex

Purkinje cellCerebellum

Axon

Axon

DendritesDendrites

Santiago Ramon y Cajal, 1900

Axon collateralsCollateralbranch

Input

Output

Electrical Signals: Ion Movement• Resting membrane potential determined by

– K+ concentration gradient– Cell’s resting permeability to K+, Na+, and Cl–

• Gated channels control ion permeability– Mechanically gated– Ligand gated– Voltage gated

Current flow through ion channels leads to changes in membrane potential

Ohm’s Law: V = I * RV = voltage, I = current (Amps), R = resistance (Ohms)

I = V/R or I = V * GG = conductance (Siemens)

For current to flow, there must be a driving force (Vm - Eion) > or < 0, thus I = (Vm - Eion) * G

If current flows across a resistance--the cell membrane acts like one--there is a change in voltage (membrane potential).

Graded potentials can be: EXCITATORY or INHIBITORY (action potential (action potential is more likely) is less likely)

The size of a graded potential is proportional to the size of the stimulus.

Graded potentials decay as they move over distance.

Graded Potentials

Graded potentials decay as they move over distance.

Cable theory

“Overshoot”

mV

+40

-80

0

1 ms

Action Potential•All-or-none•Not due to “membrane breakdown”

Shock

Na+-dependence of AP

Voltage-clamp

Voltage-clamp of squid giant axon

Isolation of Na and K currents

I/V relationship of Na and K channels

HH model

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Electrical Signals: Action Potentials

Figure 8-9 (1 of 9)

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Electrical Signals: Action Potentials

Figure 8-9 (2 of 9)

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Electrical Signals: Action Potentials

Figure 8-9 (3 of 9)

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Electrical Signals: Action Potentials

Figure 8-9 (4 of 9)

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Electrical Signals: Action Potentials

Figure 8-9 (5 of 9)

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Electrical Signals: Action Potentials

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Electrical Signals: Action Potentials

Figure 8-9 (7 of 9)

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Electrical Signals: Action Potentials

Figure 8-9 (8 of 9)

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 8-9 (9 of 9)

Electrical Signals: Action Potentials

Why is AP peak < ENa?

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Electrical Signals: Voltage-Gated Na+ Channels

Na+ channels have two gates: activation and inactivation gates

Figure 8-10a

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Electrical Signals: Voltage-Gated Na+ Channels

Figure 8-10c

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Electrical Signals: Voltage-Gated Na+ Channels

Figure 8-10d

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings

Electrical Signals: Refractory Period

Figure 8-14

How does an AP travel down an axon?

AP propagation

Figure 8-15, step 5

Speed of AP conduction is governed by:

•Diameter of the axon

•Resistance of the axon membrane to ion leakage

Myelin sheath “insulates” axons

Saltatory conduction

1 mm

Axon size matters

Myelination increases conduction velocity

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Electrical Signals: Graded Potentials

Subthreshold and suprathreshold graded potentials

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Electrical Signals: Graded Potentials

Figure 8-8b

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Electrical Signals: Coding for Stimulus Intensity

DendriteAP

trigger zoneAxon

terminal

Patch-clamp recording

Giga=109

Mega= 106

vs. sharp microelectrodePros: high resistance seal & low resistance electrode better for recording small currents and injecting large currentsCons: disrupt (“dialyze”) cellular contents

Single channel recordings“stochastic behavior”

Characterize channels by their:conductance (pS)selectivitykinetics

Whole-cell recording of different types of K channels

Channels are comprised of multiple subunits

Ligand-gated ion channels