The Journal of General Physiology, Vol 80, 1-18, Copyright © 1982 by The Rockefeller University Press
Aminopyridine block of transient potassium current
S Thompson
The blocking action of 4-aminopyridine (4-AP) and 3, 4-diaminopyridine
(Di-AP) on transient potassium current (IA) in molluscan central neurons
was studied in internal perfusion voltage-clamp experiments. Identical
blocking effects were seen when the drugs were applied either externally or
internally. It was found that aminopyridines have two kinds of effects on
IA channels. The first involves block of open channels during depolarizing
pulses and results in a shortening of the time to peak current and an
increase in the initial rate of decay of current. This effect of the drug
is similar to the block of delayed potassium current by tetraethylammonium
(TEA). The other effect is a steady block that increases in strength during
hyperpolarization, is removed by depolarization, and is dependent on the
frequency of stimulation. The voltage dependence of steady state block
approximates the voltage dependence of inactivation gating a changes e-fold
in approximately 10 mV. These data suggest that the strength of block may
depend on the state of IA gating such that the resting state of the channel
with open inactivation gate is more susceptible to block than are the open
or inactivated states. A multistate sequential model for IA gating and
voltage-dependent AP block is developed.