Mechanisms of inactivation of l-type calcium channels in human
atrial myocytes.
Sun, Hui, Normand Leblanc, Stanley Nattel.
Department of Medicine and Research Center, Montreal Heart
Institute, the Departments of Medicine and Physiology, University of
Montreal, and the Department of Pharmacology and Therapeutics, McGill
University, Montreal, Quebec H1T 1C8, Canada
APStracts 3:0471H, 1996.
We used whole cell patch-clamp and microfluorimetric (Indo-1)
techniques to measure ICa and Ca2& transients in human atrial
myocytes. During 1-s depolarizing pulses, ICa inactivation was
biexponential. The rate of rapid inactivation was slowed by
ryanodine, and was correlated with the rate of rise of [Ca2&]i (r
= 0.80, P < 0.01). Slower-phase ICa inactivation was not affected
by ryanodine, but was accelerated by increasing the availability of
Ca2& to permeate the Ca2& channel. Thus, Ca2& released
from the SR was responsible for most ICa inactivation during the
first 50 ms of a depolarization to 0 mV, and thereafter inactivation
by Ca2& permeating the channel predominated. Pure voltage
-dependent inactivation had a much slower time course of development (
> 2 s), and played a smaller role than Ca2&-dependent
mechanisms over a duration comparable to that of an action potential.
We conclude that human atrial myocytes show both voltage- and
Ca2&-dependent ICa inactivation, that Ca2&-dependent
mechanisms predominate over the time course of an action potential,
and that while both Ca2& released from the SR and Ca2&
permeating Ca2& channels play a role, SR-released Ca2& is
particularly important in early, rapid ICa inactivation while
Ca2& permeating Ca2& channels is more important in the slower
phase of Ca2&-dependent inactivation.
Received 9 August 1996; accepted in final form 15 October 1996.
APS Manuscript Number H724-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996