1. Types of Ion Channels Leak channels
some are always open (open and close randomly)
e.g., K+ leak channels cause nerve and muscle cell membranes to be more permeable to K+ than to Na+.
Gated channels (Even though the behavior of an individual channel may appear to be random, the stimulus significantly changes the probability of a population of channels being open or closed.)
voltage-gated channels
open/close due to changes in membrane potential
e.g., voltage-gated channels for Na+, K+, and Ca++
ligand-gated channels (“chemically-gated”)
open/close due to the binding (ligation) of a chemical signal (ligand)
e.g., The nicotinic cholinergic receptor opens when acetylcholine (ACh) binds to it.
mechanically-gated channels
open/close due to a mechanical stimulus
e.g., sensory receptors that respond to pressure or stretch

2. Examples of Gated Channels
e.g., voltage-gated
K+ channel
e.g., nicotinic
cholinergic receptor
Fig
Alberts et al.,
Molecular Biology of the Cell

3. Voltage-gated Na+ Channel
Fig. 14-2
Katzung, Pharmacology
Voltage-gated Na+ Channel
three states: resting, activated, and inactivated
resting
activation gate (m) closed, inactivation (h) gate open
activated
activation gate open, inactivation gate open
stimulus for opening: depolarization
time to start opening: ~ 0.1 msec
inactivated
activation gate open, inactivation gate closed
stimulus for closing: depolarization
time to start closing: ~ 0.2 msec
recovery: When the membrane returns to the resting membrane potential, the Na+ channels return to the resting state.

4. Voltage-gated K+ Channel two states: closed and open
Fig
plus Fig.11-21,
Alberts
open
stimulus for opening: depolarization
time to start opening: ~ 0.2 msec
closed
during resting state
inactivated
In some neurons (e.g., rapidly firing neurons) the K+ channel also has an inactivated state. Alberts et al., Molecular Biology of the Cell

5. Voltage-gated Na+ and K+ Channels one stimulus, three responses
/activated
Panel 11-3, Alberts et al., Molecular Biology of the Cell

6. changes in the channels
Fig altered
with channel cartoons from Katzung and Alberts
Action Potentials
changes in the channels
Stimulus
t = 0
0.1 ms
[positive feedback] ms

7. Reminder: Since depolarization, repolarization and after-hyperpolarization are due to the diffusion of Na+ and K+ through voltage-gated Na+ and K+ channels, the membrane potential cannot go higher than ENa (e.g., +60 mV) or lower than EK (e.g., –90 mV).
Moffett, Moffett and Schauf,
Human Physiology

8. Role of ATP
ATP is not directly needed for the production of an action potential.
Very few ions cross the membrane. So few that depletion of the sodium and potassium gradients takes hundreds of thousands of action potentials.
Over the long term, however, ATP energy is required to empower the Na+ pump to restore the transmembrane sodium and potassium gradients.
“battery charger” function of the sodium pump

9. Refractory Periods
Moffett, Moffett and Schauf,
Human Physiology
Fig
Absolute refractory period: No stimulus can cause an action potential.
Na+ channels become inactivated and cannot open.
Relative refractory period: A greater than normal stimulus is required in order to trigger an action potential.
The distance to threshold is greater: 1) the threshold is higher
and 2) the membrane is hyperpolarized (more negative).

10. Local Anesthetics
Local anesthetics of the “-caine” family (e.g., novocaine, benzocaine, lidocaine)
block the Na+ channel at its intracellular end. Therefore, their effect is to put the nerve cell membrane into an absolute refractory period.
anesthetic
Fig. 14.2
Katzung, Pharmacology

11. Propagation of an Action Potential
It is possible for an electrical signal to travel along an axon or a muscle cell in either direction.
Nonetheless, in neurons the signal usually travels in only one direction.
Direction of movement is determined by what area is excited first.

12. Propagation of an Action Potential
cell body and dendrites:
“receiving end”
axon terminals:
“sending end”
One end of the cell is specialized to receive signals. Action potentials start at the part of the axon closest to the receiving end.
“Active” depolarization in one place causes depolarization-to-threshold “downstream.”
“Upstream” is refractory.
The “distal” end of the cell is specialized for sending signals to the next cell.
A B C
Fig