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Encyclopedia of Physical Science and Technology EN008K-353 June 29, 2001 12:41

Ion Transport Across Biological Membranes 105

TABLE I Major Neurotransmitters of the receptor spanning the membrane. The receptor con-
sists of 5 subunits, each with a molecular weight of about
Excitatory Inhibitory
50 kiloDaltons. Together the subunits form a funnel-
O O shaped structure, projecting about 60 A above the plane of

N(CH 3 ) 3 NH 3 the membrane. The opening of the channel is about 50 A in
H 3 C O O O
diameter and narrows to a channel through the membrane
acetylcholine GABA
about 30 A in length and 8 A wide.
O O What is the relationship between the neurotransmitter

CO 2 concentration, the fraction of receptor-channels that open,
O O NH 3
the conductance of the channel, and the length of time the
NH 3
glutamate glycine channels remain open (Fig. 2)? If we can answer these
questions, and can also determine the concentration of re-
H 2 N CH 2 CH 2
ceptor sites exposed to the neurotransmitter, we can calcu-
HO
late the change in transmembrane voltage (Eqs. 1–3) and
predict whether or not a signal will be transmitted. The
NH
serotonin techniques for elucidating the mechanism of the reactions
that allow one to determine the rate of transmembrane flux
of inorganic ions and, therefore, the change in V m have
and γ -aminobutyric acid (GABA). They bind to receptors
been discussed in Section I. It is important to mention that
that form transmembrane channels that are specific for
each cell is contacted by as many as 1000 different projec-
chloride ions. They are called inhibitory receptors because
tions from other cells and each of these projections may
they shift the transmembrane potential to more negative release a different neurotransmitter from the nerve ter-
values and counteract the action of excitatory receptors. minal. The mammalian brain contains an estimated 10 12
The neurotransmitter receptors are believed to belong to cells; its information content is believed to exceed, by far,
one large family of transmembrane, channel-forming pro- that of the largest supercomputers.
teins. A three-dimensional model of the nicotinic acetyl- It appears that the techniques are now at hand to (a) in-
choline receptor from the electric organ of a fish, Tor- vestigate the kinetic mechanism of the reactions by which
pedo species, has been proposed by Nigel Unwin based
neurotransmitter receptors determine the rate of flow of
on electron diffraction images. Figure 6 gives a side view
inorganic ions across the membrane, and (b) determine
whether or not a signal will be transmitted to another cell.
The chemical mechanism of receptor-mediated transport
of inorganic ions across the membrane of neurons (nerve
cells) by a few neurotransmitter receptors has been in-
vestigated. The mechanisms by which the many receptor
isoforms facilitate the flow of inorganic ions across the
cell membrane are still unknown. Also virtually unknown
are the effects of diseases, causing mutations of receptors,
and the influence of hundreds of drugs including anticon-
vulsants, antidepressants, anesthetics, and abused drugs,
on the mechanisms.

FIGURE 6 Three-dimensional model of the nicotinic acetyl-
choline-gated ion channel. The structure is based on a three- V. INORGANIC ION TRANSPORT AND
dimensional reconstruction of electron microscope images by Un- THE RAPID TRANSMISSION OF
win and his colleagues. The receptor-channel complex consists
ELECTRICAL SIGNALS OVER LONG
of five subunits, all of which contribute to forming the pore. When
DISTANCES (UP TO ∼1 m)
two molecules of acetylcholine bind to portions of the α-subunits
exposed to the membrane surface, the receptor-channel changes
conformation. This opens a pore in the portion of the channel em- The movement of inorganic ions across a cell membrane
bedded in the lipid bilayer, and both K and Na flow through the that initiates an electrical signal is only one step in signal
+
+
open channel down their electrochemical gradients. (Reproduced
with permission from Kandel, E. R., Schwartz, J. H., and Jessel, T. transmission in organisms. The rapid transmission of this
M. (2000). “Principles of Neuronal Science,” 4th edition. McGraw signal, over distances of up to 1 m, by the axon of cells is
Hill, New York.) discussed next.