Bi/CNS 150 Lecture 4
Monday, October 6, 2013
Action potentials
Henry Lester
If you’ve not requested a section, email Teagan
1
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
Prof. David McCormick’s data
http://info.med.yale.edu/neurobio/mccormick/movies/rly_exp.avi
Intracellular recording with sharp glass electrodes.
2. Artificially applied acetylcholine acts on muscarinic receptors to
change the membrane potential, increasing action potential
frequency.
V
Prof. David McCormick’s data
http://info.med.yale.edu/neurobio/mccormick/movies/ach_fin.avi
(The spikes in these examples are about 100 mV in amplitude)
Monday’s lecture employs electrical circuits
http://www.krl.caltech.edu/Projects/physicscourses/index.htm
See also Appendix A in Kandel
4
Atomic-scale structure of (bacterial) Na+ channels (2011, 2012)
Views
from the
extracellular
solution
electrically, open channel
=
conductor
Views
from the
membrane
plane
5
The miniature single-channel conductors add in parallel
GNa = SgNa
GK = SgK
outside
GNa
GK
=
ENa
EK
(- 60 mV)
gK
gNa
(+60 mV)
cytosol = inside
gNa
mostly Na+
mostly K+
gK
6
The membrane potential at steady state
(not at equilibrium)
At DC,
IC = CdV/dt = 0,
so
outside
Na+
K+
Cl-
resting
potential:
K+ channels
open
peak of
action
potential:
Na+ channels
open too
G
C
E
cytosol = inside
E K GK + E NaGNa + ECl GCl
DV =
GK + GNa + GCl
“after-hyperpolarization”:
more K+ channels open
7
Simulation of the nerve impulse (“unclamped”)
Francisco Bezanilla's simulation program at the Univ of Chicago:
http://nerve.bsd.uchicago.edu/
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Simulation of the nerve impulse (“unclamped”)
Spatially homogeneous membrane (“membrane AP”).
Either spherical, or patch, or wire in axon.
First, show passive properties of membrane
Turn 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 mA).
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 mA. Plot G(K)
simultaneously.
9
Simulation of the nerve impulse (“unclamped”)
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.)
10
Cable properties of the Axon
Francisco Bezanilla's simulation program at the Univ of Chicago:
http://nerve.bsd.uchicago.edu/nerve1.html
Click on Voltage Plot, V vs T.
Start
Parameter edits are not useful.
11
Simulation of the nerve impulse (“unclamped”)
http://nerve.bsd.uchicago.edu/nerve1.html
Propagation
(V vs. t)
Measure propagation velocity: set blue electrode at 2 cm
6.18 ms – 3.88 ms = 2.3 ms
30 mm/2.3 ms = 11 mm/ms = 13 m/s. Pretty fast!
At 30o C, 2.89 ms - 1.47 ms = 1.42 ms
30 mm / 1.42 ms = 21.1 m/s. Faster
12
There are dozens of V-gated channels,
Causing the variety of action potential waveforms
13
An approximate explanation for the electrocardiogram, slide 1
The left ventricle pumps against the greatest resistance
therefore it has thickest walls;
therefore its currents are the largest;
therefore it contributes most of the ECG.
14
An approximate explanation for the electrocardiogram, slide 2
The capacitive currents are largest
dV
I =C
+  (V  Ei ) gi ;
dt
i
i = Na, K , Cl
An extracellular
DVext = IRext
Rext
electrode pair
records IR drops
proportional to the
(absolute value) of
extracellular
Na+
K+
Cl-
Na+
K+
Cl-
the 1st derivative of
G
membrane potential.
C
G
C
E
E
cytosol
15
An approximate explanation for the electrocardiogram, slide 3
DVext = IRext
Rext
chest
Only a small fraction of the current
flows across the resistance between
chest and a limb.
This produces a DV ~
times
smaller than the transmembrane
potential.
103
The ECG records this signal
DVext = IRext
Rext
C
extracellular
Na+K C
+ lG
E
intracellular
Na+K C
+ l-
C
G
E
leg
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Action potentials and the electrocardiogram
Na+ channels conduct
K+ channels conduct
Action Potential
measured with
intracellular
electrode
~ 100 mV
~ 1 sec
R
Electrocardiogram
measured
on the skin
~ 100 mV
T
P
QS
ST depression is a common anomaly,
implying that additional current flows between sections of the heart
during the “plateau”
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The frequency of impulses represents signaling among cells
in the
nervous system.
-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
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End of Lecture 4
19
Intracellular recording with sharp glass electrodes
A cell is receiving stimuli from other cells, not from the experimenter
http://info.med.yale.edu/ne
urobio/mccormick/movies/rl
y_exp.mpg
V
Same data;
choice of formats.
Media player required
http://info.med.yale.edu/neu
robio/mccormick/movies/rly
_exp.avi
(The spikes in these examples are about 100 mV in amplitude)
20