FREE ESSAY ON A SUMMARY: ION CHANNELS IN THE NERVE-CELL MEMBRANE

A SUMMARY: ION CHANNELS IN THE NERVE-CELL MEMBRANE

A Summary: Ion Channels in the Nerve-Cell Membrane
In this article, Richard D. Keynes details the workings of ion channels in nerve cell
membranes. Nerve impulses (action potentials) are the unit by which information travels
in an organism's nervous system, and the generation of this action potential is dependent
on the nerve membrane being permeable to ions which in turn makes said membrane
excitable. Electrical activity of a nerve is triggered by a depolarization across the
membrane and this also causes the sodium channels to open and allow sodium ions to flow
inward due the electrochemical gradient. Eventually, the membrane potential falls to
zero, the sodium channels close, and potassium channels open allowing potassium ions back
in to the cell thus restoring the resting potential. It is this exchange of ions that
provided the immediate energy for the propagation of a nerve impulse. The experimental
technique that illustrated the different activities and timing of the opening and closing
of sodium and potassium channels was the use of voltage-clamps. Voltage-clamps allowed
researchers to hold an axon at a predetermined membrane potential and observe the
behavior of the ion channels at those levels. 
Voltage-clamping has also been employed in the study of the selectivity of ion channels.
Bertil Hille collected evidence of four energy barriers in a sodium channel that prevent
other ions from passing through and only allow one sodium ion through at a time. The
highest of these barriers results from the fact that sodium ions readily lose their
stabilizing water molecules when they interact with the ionized carboxylic acid groups in
the channel wall and are thus able to pass through the channel. On the other hand, the
larger potassium ions do not interact correctly with the carboxylic acid group and
therefore cannot surmount the energy barrier to pass through. Hille also proposed that
the electronegative and conformational properties of the molecules in the sodium channel
also contribute to its selectivity.
Two important tools in the study of sodium channels and their voltage-sensitive gating
mechanism have been the nerve poisons, tetrodotoxin and saxitoxin. These two toxins bind
specifically to sodium channels and effectively block them. Because only one molecule of
each toxin binds to each sodium channel, these toxins were used in a bioassay to count
the number of sodium channels on the membrane of an axon. Results proved that small axons
have the fewer sodium channels per square micrometer than large axons. This result also
satisfied previous calculations of how many channels would be necessary to obtain the
maximum conduction velocity in a 500 micrometer axon. Tetrodotoxin has also been
enormously valuable in the study of ionic gating. The mechanism that controls the opening
and closing of ion channels involves the movement of charged particles that result in a
small charge displacement. However since this gating 
Ayele, 2
current is so much smaller that the ionic current through the channel, it was nearly
impossible to measure. Tetrodotoxin enables this measurement by blocking the sodium
channels (potassium ions are also blocked in this experiment) and stopping the ionic
current, while still allowing the opening and closing of the sodium channels. Using this
technique, the gating current was found to rise and then fall to zero when the
(approximately) three or four charged particles reached their new configuration. The
mechanism that closes the sodium channels was found to be electrically silent. 
Sodium channels appear to have three operational states. They are either at rest,
conducting, or inactivated. The molecular model of a sodium channel has not yet been
described however. This is due the many complexities of the channel including its complex
kinetics, and hydrophobic and hydrophilic proteins, that make analyzing the channel
molecules difficult. Potassium channels, while just as important as sodium channels, are
even more difficult to study. This is due the fact that there is no analogue of
tetradotoxin for potassium channels, and because their opening has a ten second delay,
and is much slower than that of sodium channels. This makes gating current measurements
nearly impossible to obtain. However, some studies on electrical noise have provided the
estimate that there is perhaps one potassium channel for every 10 sodium channels in an
axon's membrane.
There are three types of currents described in the article: ionic current, gating
current, and displacement current. Ionic current is the measure of the charge flow that
results from the movement of ions (sodium and potassium) through ion channels in the cell
membrane, and involves 100 sodium ions in one nerve impulse. The gating current is much
smaller than the ion current, it only involves the transfer of about four electronic
charges, and it is the measure of the gating particles as they move to their "open"
configuration. The gating current is induced by depolarization of the nerve cell. The
displacement current in a nerve cell is composed mostly of the gating current but is also
partly due to the, "charging and discharging of the large static capacity of the
membrane." This current is recorded when the potential of a voltage-clamped cell is
suddenly altered with a pulse. By comparing the displacement current values resulting
from hyperpolarizing and depolarizing pulses, the gating current can be deducted from the
total displacement current.