BioPHYSICAL chemistry

a domino effect. In addition, the dipoles of small
helices appear to contribute electrostatically to the
selectivity, with the dipoles for the K+ channel
aligned but the homologous helices for the Cl−
channel being antiparallel.
An example of a ligand-gated channel is the
acetylcholine receptor that mediates the transmis-
sion of nerve signals across synapses by the neuro-
transmitter acetylcholine. The arrival of a wave of
membrane depolarization at the synapse leads to
a release of acetylcholine into the synapse. The
acetylcholine depolarizes the postsynaptic mem-
brane by increasing the conductance of Na+and K+
and correspondingly triggers an action potential.
This change in ion permeability is defined by the
acetylcholine receptor, which serves as a ligand-gated
channel and the ion conductance, which is regu-
lated by the binding of acetylcholine. The nicotinic
acetylcholine receptor belongs to a superfamily that
also contains receptors for the neurotransmitters
serotonin, γ-aminobutyric acid (GABA), glycine, and
glutamate. The N-terminal 230 or so amino acids of each
receptor form the agonist-binding domain. This region,
as well as binding neurotransmitters, also binds mole-
cules of importance in human and veterinary medicine.
The structure of the acetylcholine receptor has been
determined to a limited resolution by electron micro-
scopy (Figure 18.11). This receptor is a pentamer with
two binding sites for acetylcholine. The receptor has
a cylindrical appearance with an approximately 5-fold
symmetry formed by the five protein subunits. At the
center of the cylinder is a channel 10 –20 Å in diameter.
In response to the binding of acetylcholine, the channel
opens. The transport of ions through the channel is deter-
mined by the presence of several negatively charged
amino acids in the center of the channel that prevent
the transport of anions and limit the transport of cations
by size exclusion.
Whereas the determination of the structure at an
atomic level remains elusive, a structure has been
determined for a water-soluble protein that binds
acetylcholine (Figure 18.12). The acetylcholine protein
is synthesized in glial cells located in the brains of snails
and released in the synaptic cleft. The protein regulates
interneurological transmission by binding acetylcholine

CHAPTER 18 MEMBRANE POTENTIALS 401

Synaptic

side

Cytosolic

side

Figure 18.11Overall structure of the

nicotinic acetylcholine receptor showing

the pentameric arrangement of the subunits

and central channel. Modified from Unwin

(1993).

D

E

A

B

C

Figure 18.12Structure of the

water-soluble acetylcholine-binding

homopentamer (individual subunits

are labeled A through E). This protein

is structurally homologous to the

acetylcholine-binding extracellular

domain of the acetylcholine receptor.

Modified from Brejc et al. (2001).