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Bi/CNS 150 Lecture 4

Monday, October 6, 2013

Action potentials

Henry Lester

If you’ve not requested a section, email Teagan

Electricity is also a Language of the Brain.Intracellular recording with sharp glass electrodes.

1. A current applied by the experimenter increases firing rates

V, I

http://info.med.yale.edu/neurobio/mccormick/movies/rly_exp.avi

Prof. David McCormick’s data

Intracellular recording with sharp glass electrodes.2. Artificially applied acetylcholine acts on muscarinic receptors to

change the membrane potential, increasing action potential frequency.

(The spikes in these examples are about 100 mV in amplitude)

http://info.med.yale.edu/neurobio/mccormick/movies/ach_fin.avi

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Prof. David McCormick’s data

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http://www.krl.caltech.edu/Projects/physicscourses/index.htm

Monday’s lecture employs electrical circuits

See also Appendix A in Kandel

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Atomic-scale structure of (bacterial) Na+ channels (2011, 2012)

Views from the

extracellular solution

electrically, open channel = conductor

Views from the

membrane plane

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The miniature single-channel conductors add in parallel

ENa

(+60 mV)

GNa = Na

=GNa

Na

Na

outside

cytosol = inside

mostly K+mostly Na+

GK = K

EK (- 60 mV)

GKK

K

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C

E

G

Na+

VE G E G E G

G G GK K Na Na Cl Cl

K Na Cl

K+

At DC, IC = CdV/dt = 0,

so

Cl-

peak of action

potential: Na+ channels

open too

resting potential:

K+ channels open

outside

cytosol = inside

The membrane potential at steady state(not at equilibrium)

“after-hyperpolarization”: more K+ channels open

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http://nerve.bsd.uchicago.edu/

Simulation of the nerve impulse (“unclamped”)

Francisco Bezanilla's simulation program at the Univ of Chicago:

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Spatially homogeneous membrane (“membrane AP”). Either spherical, or patch, or wire in axon.

First, show passive properties of membraneTurn off conductances. Ampl ± 2, delay 10, duration 15, total time 40

Now back to default (“reset parameters”)Note threshold. Vary pulse amplitude (2 to 20 A).Note constant amplitude

Note hyperpolarization. Plot G(K), G(Na) and note that hyperpolarization is caused by G(K).

“Refractory” period 30 ms total time, vary pulse 2 duration, pulse 3 = 30 A. Plot G(K)

simultaneously.

Simulation of the nerve impulse (“unclamped”)

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Repetitive firing: the frequency code

total time to 40 ms; lengthen pulse 1 to 30 ms,

Vary pulse amp from 2, 5, 10.

Note the smaller AP’s—the squid axon is not specialized for repetitive

firing.

(For robust frequency encoding, we require at least one additional type of K+ channel.)

Simulation of the nerve impulse (“unclamped”)

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http://nerve.bsd.uchicago.edu/nerve1.html

Click on Voltage Plot, V vs T.StartParameter edits are not useful.

Cable properties of the Axon

Francisco Bezanilla's simulation program at the Univ of Chicago:

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http://nerve.bsd.uchicago.edu/nerve1.html

Propagation (V vs. t)

Measure propagation velocity: set blue electrode at 2 cm6.18 ms – 3.88 ms = 2.3 ms30 mm/2.3 ms = 11 mm/ms = 13 m/s. Pretty fast!

At 30o C, 2.89 ms - 1.47 ms = 1.42 ms30 mm / 1.42 ms = 21.1 m/s. Faster

Simulation of the nerve impulse (“unclamped”)

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There are dozens of V-gated channels,Causing the variety of action potential waveforms

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An approximate explanation for the electrocardiogram, slide 1

The left ventricle pumps against the greatest resistancetherefore it has thickest walls; therefore its currents are the largest; therefore it contributes most of the ECG.

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An approximate explanation for the electrocardiogram, slide 2

CE

G

Na+ K+ Cl-extracellular

cytosol

CE

G

Na+ K+ Cl-

ClKNai

gEVdt

dVCI

iii

,,

;)(

extRextext IRV

The capacitive currents are largest

An extracellular

electrode pair

records IR drops

proportional to the

(absolute value) of

the 1st derivative of

membrane potential.

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chest

leg

extRextext IRV

Only a small fraction of the current flows across the resistance between chest and a limb.

This produces a V ~ 103 times smaller than the transmembrane potential.

The ECG records this signal

An approximate explanation for the electrocardiogram, slide 3

CE

G

Na+K+

Cl-

extracellular

intracellular

CE

G

Na+K+

Cl-

extRextext IRV

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Action potentials and the electrocardiogram

Electrocardiogrammeasured on the skin

Action Potentialmeasured with

intracellularelectrode

P

S

R

T

Q

K+ channels conductNa+ channels conduct

~ 100 V

~ 100 mV

~ 1 sec

ST depression is a common anomaly,implying that additional current flows between sections of the heart during the “plateau”

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-from sense organs to the brain

-within the brain

-from the brain to muscles

-even in a muscle or in the heart

-even in the pancreas

The frequency of impulses represents signaling among cells

in the

nervous system.

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End of Lecture 4

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Intracellular recording with sharp glass electrodesA cell is receiving stimuli from other cells, not from the experimenter

(The spikes in these examples are about 100 mV in amplitude)

Same data;choice of formats.

Media player required

http://info.med.yale.edu/neurobio/mccormick/movies/rly_exp.mpg

http://info.med.yale.edu/neurobio/mccormick/movies/rly_exp.avi

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