Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

channels and the electrical PROPERTIES of membranes
623
stimulating
current
(A)
0 1 2
EXTRACELLULAR
SPACE
CYTOSOL
CLOSED
+ + +
+ + +
–––
+
+
+
+
–––
voltage-gated
Na + channel
plasma
membrane
at rest
50
membrane
potential (mV)
0
-50
– – –
– – –
+
+
+ + +
+ + +
+
+
membrane
refractory
– – –
– – –
+
+
+ + +
+ + +
+
+
membrane
depolarized
(B)
0 1 2
time (milliseconds)
closed open inactivated closed
(C)
INACTIVATED
OPEN
Figure 11–30 Na + channels and an action potential. (A) An action potential is triggered by a brief pulse of current, which
(B) partially depolarizes the membrane, as shown in the plot of membrane potential versus time. The green curve shows how
the membrane potential would have simply relaxed back to the resting value after the initial depolarizing stimulus if there had
been no voltage-gated Na + channels in the membrane. The red curve shows the course of the action potential that is caused
by the opening and subsequent inactivation of voltage-gated Na + channels. The states of the Na + channels are indicated
in (B). The membrane cannot fire a second action potential until the Na + channels have returned from the inactivated to the
closed conformation; until then, the membrane MBoC6 m11.29/11.31
is refractory to stimulation. (C) The three states of the Na + channel. When the
membrane is at rest (highly polarized), the closed conformation of the channel has the lowest free energy and is therefore most
stable; when the membrane is depolarized, the energy of the open conformation is lower, so the channel has a high probability
of opening. But the free energy of the inactivated conformation is lower still; therefore, after a randomly variable period spent in
the open state, the channel becomes inactivated. Thus, the open conformation corresponds to a metastable state that can exist
only transiently when the membrane depolarizes (Movie 11.10).
the repetitive firing rate of a neuron. The cycle from initial stimulus to the return
to the original resting state takes a few milliseconds or less. The Na + channel can
therefore exist in three distinct states—closed, open, and inactivated—which contribute
to the rise and fall of the action potential (Figure 11–30).
This description of an action potential applies only to a small patch of plasma
membrane. The self-amplifying depolarization of the patch, however, is sufficient
to depolarize neighboring regions of membrane, which then go through the same
cycle. In this way, the action potential sweeps like a wave from the initial site of
depolarization over the entire plasma membrane, as shown in Figure 11–31.
The Use of Channelrhodopsins Has Revolutionized the Study of
Neural Circuits
Channelrhodopsins are photosensitive ion channels that open in response to
light. They evolved as sensory receptors in photosynthetic green algae to allow
the algae to swim toward light. The structure of channelrhodopsin closely resembles
that of bacteriorhodopsin (see Figure 10–31). It contains a covalently bound
retinal group that absorbs light and undergoes an isomerization reaction, which
MBoC6 m11.21/11.19
triggers a conformational change in the protein, opening an ion channel in the
plasma membrane. In contrast to bacteriorhodopsin, which is a light-driven proton
pump, channelrhodopsin is a light-driven cation channel.
Using genetic engineering techniques, channelrhodopsin can be expressed
in virtually any cell type in vertebrates and invertebrates. Researchers first
introduced the gene into cultured neurons and showed that flashing light could
now activate the channelrhodopsin and induce the neurons to fire action potentials.
Because the frequency of the light flashes determined the frequency of the
action potentials, one can control the frequency of neuronal firing with millisecond
precision.
Next, neurobiologists used the approach to activate specific neurons in the
brain of experimental animals. Using a tiny fiber optic cable implanted near the