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

632 Chapter 11: Membrane Transport of Small Molecules and the Electrical Properties of Membranes
by blocking the acetylcholine receptors on skeletal muscle cells with curare, a
plant-derived drug that was originally used by South American Indians to make
poison arrows. Most drugs used to treat insomnia, anxiety, depression, and
schizophrenia exert their effects at chemical synapses, and many of these act
by binding to transmitter-gated channels. Barbiturates, tranquilizers such as
Valium, and sleeping pills such as Ambien, for example, bind to GABA receptors,
potentiating the inhibitory action of GABA by allowing lower concentrations of
this neurotransmitter to open Cl – channels. Our increasing understanding of the
molecular biology of ion channels should allow us to design a new generation of
psychoactive drugs that will act still more selectively to alleviate the miseries of
mental illness.
In addition to ion channels, many other components of the synaptic signaling
machinery are potential targets for psychoactive drugs. As mentioned earlier, after
release into the synaptic cleft, many neurotransmitters are cleared by reuptake
mechanisms mediated by Na + -driven symports. Inhibiting such transporters prolongs
the effect of the neurotransmitter, thereby strengthening synaptic transmission.
Many antidepressant drugs, including Prozac, inhibit the reuptake of serotonin;
others inhibit the reuptake of both serotonin and norepinephrine.
Ion channels are the basic molecular units from which neuronal devices for
signaling and computation are built. To provide a glimpse of how sophisticated
these devices can be, we consider several examples that demonstrate how the
coordinated activities of groups of ion channels allow you to move, feel, and
remember.
Neuromuscular Transmission Involves the Sequential Activation of
Five Different Sets of Ion Channels
The following process, in which a nerve impulse stimulates a muscle cell to contract,
illustrates the importance of ion channels to electrically excitable cells. This
apparently simple response requires the sequential activation of at least five different
sets of ion channels, all within a few milliseconds (Figure 11–39).
1. The process is initiated when a nerve impulse reaches the nerve terminal
and depolarizes the plasma membrane of the terminal. The depolarization
transiently opens voltage-gated Ca 2+ channels in this presynaptic membrane.
As the Ca 2+ concentration outside cells is more than 1000 times
RESTING NEUROMUSCULAR JUNCTION
ACTIVATED NEUROMUSCULAR JUNCTION
acetylcholinegated
cation
channel
nerve terminal
acetylcholine
in synaptic
vesicle
Ca 2+
nerve
impulse
voltage-gated
Na + channel
voltage-gated
Ca 2+ channels
3
2
1
Na + Na +
4
sarcoplasmic
reticulum
Ca 2+ -release
channel
5
Ca 2+
Figure 11–39 The system of ion
channels at a neuromuscular junction.
These gated ion channels are essential for
the stimulation of muscle contraction by a
nerve impulse. The various channels are
numbered in the sequence in which they
are activated, as described in the text.