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

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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 ions across the cell membrane AND the differential permeability of the membrane to these ions

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Page 1: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Page 2: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Channels allow ions to diffuse across membranes

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

Page 3: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Figure 5-34a

Potassium Equilibrium Potential

Page 4: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Figure 5-34b

Page 5: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Figure 5-34c

Resting membrane potential is due mostly

to high potassium permeability

Page 6: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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).

Page 7: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Page 8: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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Typical ion concentrations

Page 9: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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]

Page 10: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Sodium Equilibrium Potential

ENa = 61 x 1 = +61 mV

ENa 61

1 log

[150]

[15]

Page 11: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Page 12: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

• 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

Page 13: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Real neurons and “Dynamic Polarization”

Pyramidal cellLayer V neocortex

Purkinje cellCerebellum

Axon

Axon

DendritesDendrites

Santiago Ramon y Cajal, 1900

Axon collateralsCollateralbranch

Input

Output

Page 14: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Page 15: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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).

Page 16: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Page 17: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Graded potentials decay as they move over distance.

Page 18: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Cable theory

Page 19: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

“Overshoot”

mV

+40

-80

0

1 ms

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

Shock

Page 20: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Na+-dependence of AP

Page 21: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Voltage-clamp

Page 22: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Voltage-clamp of squid giant axon

Page 23: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Isolation of Na and K currents

Page 24: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

I/V relationship of Na and K channels

Page 25: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

HH model

Page 26: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Electrical Signals: Action Potentials

Figure 8-9 (1 of 9)

Page 27: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Electrical Signals: Action Potentials

Figure 8-9 (2 of 9)

Page 28: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Electrical Signals: Action Potentials

Figure 8-9 (3 of 9)

Page 29: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Electrical Signals: Action Potentials

Figure 8-9 (4 of 9)

Page 30: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Electrical Signals: Action Potentials

Figure 8-9 (5 of 9)

Page 31: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Copyright © 2007 Pearson Education, Inc., publishing as Benjamin Cummings Figure 8-9 (6 of 9)

Electrical Signals: Action Potentials

Page 32: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Electrical Signals: Action Potentials

Figure 8-9 (7 of 9)

Page 33: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Electrical Signals: Action Potentials

Figure 8-9 (8 of 9)

Page 34: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Electrical Signals: Action Potentials

Why is AP peak < ENa?

Page 35: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Electrical Signals: Voltage-Gated Na+ Channels

Na+ channels have two gates: activation and inactivation gates

Figure 8-10a

Page 36: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Electrical Signals: Voltage-Gated Na+ Channels

Figure 8-10c

Page 37: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Electrical Signals: Voltage-Gated Na+ Channels

Figure 8-10d

Page 38: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Electrical Signals: Refractory Period

Page 39: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Figure 8-14

How does an AP travel down an axon?

Page 40: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

AP propagation

Page 41: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical
Page 42: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical
Page 43: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical
Page 44: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Figure 8-15, step 5

Page 45: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Speed of AP conduction is governed by:

•Diameter of the axon

•Resistance of the axon membrane to ion leakage

Page 46: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Myelin sheath “insulates” axons

Page 47: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Saltatory conduction

Page 48: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

1 mm

Axon size matters

Page 49: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Myelination increases conduction velocity

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are needed to see this picture.

Kawasaki Z750S

Top speed=170 mphTop speed=225 mph

Page 50: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Electrical Signals: Graded Potentials

Subthreshold and suprathreshold graded potentials

Page 51: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Electrical Signals: Graded Potentials

Figure 8-8b

Page 52: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Electrical Signals: Coding for Stimulus Intensity

DendriteAP

trigger zoneAxon

terminal

Page 53: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

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

Page 54: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Single channel recordings“stochastic behavior”

Characterize channels by their:conductance (pS)selectivitykinetics

Page 55: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Whole-cell recording of different types of K channels

Page 56: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Channels are comprised of multiple subunits

Page 57: Resting membrane potential 1 mV= 0.001 V membrane separates intra- and extracellular compartments inside negative (-80 to -60 mV) due to the asymmetrical

Ligand-gated ion channels