1. CSF
Cerebrospinal Fluid (CSF)
Neurons are surrounded by an aqueous saline solution called
cerebrospinal fluid (CSF).
The CSF contains sodium (Na+), potassium (K+), chloride (Cl-), and
other ions in solution.
The neuronal membrane itself (lipid bilayer) is impermable to the
movement of ions. However, ions can cross the membrane by two
means...
2. Transporters and Channels Move Ions Across the Neuronal Membrane
Ion Transporters
Ion Channels
3. The Na+/K+ pump
4. Restiing Potential
The Resting Potential
The resting potential is negative because:
1. The K+ concentration is greater inside than outside the neuron,
due to the action of the sodium / potassium transporter “pump.”
2. At rest, the neuron is primarily permeable to K+, because the
membrane contains K+ “leak” ion channels.
5. Diffusion and electrostatic (Coulomb) force
Two Physical Phenomena Establish the
Resting Potential
Diffusion: K+ diffuses out down its concentration gradient.
Electrostatic force: As K+ diffuses out, the inside
becomes negative compared to the outside. Eventually, K+
is attracted strongly enough to the negative inside that the
diffusion stops. (Opposite charges attract).
6. Coulomb’s Law
Electrostatic force (Coulomb’s Law)
(Opposite charges attract)
(q1 )(q2 )
F"
2
r
7. Nernst Equation
The Nernst Equation
(
)
E x = 58 log [x] out
z
[x] in
Ex
Equilibrium potential for ion x
[x] out
Outside concentration
[x] in
Inside concentration
z
Electric charge (valence of the ion)
8. Logarithm Review
Logarithm Review
log(n)
★
0
Log(1) = 0, because 10 = 1
1
Log(10) = 1, because 10 = 10
-1
Log(0.1) = -1, because 10 = 0.1
☆
When n = 1, log(n) is 0
n > 1, log(n) is positive (★)
n < 1, log(n) is negative (☆)
n
9. Electrochemical Equilibrium for K+ Ions - an example
ground (Vout = 0)
K+
Cl-
(reference location)
10. Electrochemical Equilibrium for K+ Ions - another example
ground (Vout = 0)
K+
Cl-
(reference location)
11. Electrochemical Equilibrium
K+
Na+
Cl-
12. Ionic Concentrations and Equilibrium Potentials
(
)
E x = 58 log [x] out
z
[x] in
Inside (mM)
Outside (mM)
Ex (mV)
Potassium (K+)
140
5
-84
Sodium (Na+)
10
145
+67
At rest, the neuron is primarily permeable to K+, so the resting
potential is close to the K+ equilibrium potential: negative!
13. Goldman Equation
The Goldman Equation
(
V m = 58 log Pk [k] out + P Na [Na] out
Pk [k] in + P Na [Na] in
Px
)
Permeability to ion x
The resting potential is -65 mV, not -84 mV, because there is
some permeability to Na+, even at rest. So some Na+ is
continually flowing into the neuron at rest, and some K+
flowing out.
14. Receptor Potential Causing Action Potenial
Vm (mV)
Receptor (generator) potential
threshold
Action potential
(spike)
Membrane Potential (mV)
15. Synaptic Potentials Causing Action Potential
0
2
4
6
Time (ms)
16. Action Potential
Membrane Potential (mV)
The Action Potential
50
0
-50
-65
(“polarized”)
rising phase
falling phase
threshold
resting potential
strong receptor or 0
synaptic potential
(“depolarization”)
undershoot
(“afterhyperpolarization”)
1
2
Time (ms)
17. Voltage-Gated Sodium Channel
The Voltage-Gated Sodium Channel
gating charge
+
3) channel opens
Na+
1) sensory receptor
or synaptic activity
Na+
Axon
2) depolarization
18. Action Potential Rising Phase
The action potential rising phase occurs because the neuronal
membrane contains voltage-gated Na+ channels that open in a
regenerative manner if depolarization passes the threshold level:
Na+ rushes in
POSITIVE
FEEDBACK
LOOP
strong receptor
potential or synaptic potential
voltage-gated Na+
channels open
19. Voltage-Gated Sodium Channel
The “Real” Voltage-Gated Sodium
Channel Has Two Gates
+
ga tiv
te ati
on
in
ga act
te iva
tio
n
Na+
ac
+
Axon
Na+
20. Voltage-Gated Sodium Channel
The Voltage-Gated Sodium Channel Has
Three States
closed
open
inactivated
+
+
+
+
+
+
Axon
21. End of Rising Phase
The action potential rising phase ends because
the voltage-gated Na+ channels inactivate
Na+ no
longer
enters
voltage-gated Na+
POSITIVE
channels
LOOP
inactivate
ENDS
22. Voltage-Gated Sodium Channel
The Voltage-Gated Potassium Channel
gating charge
+
3) K+ channel
opens, K+ leaves
“Creaky” door (slow)
1) Na+ entry
(rising phase)
Na+
K+
Axon
2) depolarization
23. Action Potential Falling Phase
Na+ no
longer
enters
The action potential falling
phase occurs because the
voltage-gated K+ channels
open (with a delay) in
response to depolarization.
POSITIVE
LOOP
ENDS
voltage-gated Na+
channels
inactivate
NEGATIVE
FEEDBACK
voltage-gated K+
LOOP
channels open
K+ flows out
Membrane Potential (mV)
24. Action Potential
end of rising phase
Na+ channels inactivate;
Na+ stops entering
50
0
-50
-65
rising phase
Na+ channels open;
Na+ enters
falling phase
K+ channels open;
K+ leaves
threshold
resting potential
undershoot
0
1
2
Time (ms)
25. Action Potential
Action Potential Summary
1. The membrane is depolarized past threshold, by a receptor
potential or synaptic potential.
2. Voltage-gated sodium channels open in a positive-feedback
loop, causing the rising phase.
3. The sodium channels inactivate, ending the rising phase
and initiating the refractory period.
4. Voltage-gated potassium channels open, causing the falling
phase and the undershoot (after-hyperpolarization).
5. The sodium channels close, ending the refractory period.
6. The potassium channels close, ending the undershoot and
restoring the membrane to its resting potential.
26. Action Potential
voltage-gated Na+ channels
refractory
closed
open
inactivated
closed
+
+
+
+
+
+
+
+
time
velocity
voltage
+
closed
voltage-gated K+ channels
+
+
closed
+
open
closed
27. Importance of The Refractory Period
The Refractory Period
1. Ensures unidirectional (“polarized”) action potential
conduction, away from the cell body.
2. Places an upper limit on the firing rate of a neuron.
28. Importance of The Refractory Period
Unidirectional Conduction
Under normal conditions, action potentials only move in one
direction: away from the cell body.
This is not due to an intrinsic property of the axon. It is due
to the refractory period.....
Normally, the action potential only moves away from the cell body, because it
starts there, so the refractory “wake” prevents it from going backwards.
Note: Cell body is to left; axon terminal is to right