Chapter 3: VoltageDependent Membrane Permeability
Ionic Currents Across Nerve Cell Membranes
1. A transient increase in the permeability of the neuronal membrane to Na initiates
the action potential.
2. A key to understanding this phenomenon is the observation that action potentials
are initiated only when the neuronal membrane potential becomes more positive
than a threshold level.
1. This+observation suggests that the mechanism responsible for the increase in
Na permeability is sensitive to the membrane potential.
3. The fact that the Na permeability that generates the membrane potential change
is itself sensitive to the membrane potential presents both conceptual and
practical obstacles to studying the mechanisms underlying the action potential.
1. A practical problem is the difficulty of systematically varying the membrane
potential to study the permeability change, because such changes in
membrane potential will produce an action potential, which causes further,
uncontrolled changes in the membrane potential.
4. Voltage clamp method: a technique that uses electronic feedback to
simultaneously control the membrane potential of a cell and measure the trans
membrane currents that result from the opening and closing of ion channels.
5. In the late 1940s, Alan Hodgkin and Andrew Huxley used the VC technique to
work out the permeability changes underlying the action potential.
1. They were the+ irst i+vestigators to test directly the hypothesis that potential
sensitive Na and K permeability changes are both necessary and sufficient
for the production of action potentials.
1. The fact that membrane depolarization elicits these ionic currents
establishes that the membrane permeability of axons is indeed voltage
Two Types of VoltageDependent Ionic Currents
6. The results demonstrate that the ionic permeability of neuronal membranes is
voltagesensitive, but the experiments don’t identify how many types of
permeability exist, or which ions are involved.
7. The voltage sensitivity of the early current gives an important clue about the
nature of the ions carrying the currentnamely no current flows when the
membrane potential is clamped at +52 mV. +
1. For the squid neurons studied by Hodgkin and Huxley, the external Na
concentration is 440 mM, and the internal Na concentration is 50 mM.
8. Removal of external Na has little effect on the outward current that flows after
the neuron has been kept at a depolarized membrane voltage for several
1. This further result shows that the late, outwards current must be due to the
flow of an ion other than Na .
1. Several lines of evidence present Hodgkin, Huxley and others showed that
this outwards current is caused by K exiting neuron. 9. Taken together, these experiments show that changing the membrane potential to
a level more positive that the resting potential produces two effects: an early
influx of Na into the neuron, followed by a delayed efflux of K .
1. The early influx of Na produces a transient inward current, whereas the
delayed efflux of K produces a sustained outward current.
1. The differences in the time course and ionic sensitivity of the two fluxes
suggest that two different ionic permeability mechanisms are activated by
changes in membrane potential.
2. The differential sensitivity of Na and K currents to these drugs provides
strong additional evidence that Na and K flow through independent
3. Tetrodotoxin, tetraethylammonium, and other drugs that interact with specific
types of ion channels have been extraordinarily useful tools in characterizing
these channel proteins.
Two VoltageDependent Membrane Conductances
10. Membrane conductance: the reciprocal of membrane resistance. Changes in
membrane conductance results from, and are used to describe, the opening or
closing of ion channels.
1. Closely related, although not identical to membrane perm