Nifedipine inhibits the movement of cardiac calcium channels
through late, but not early gating transitions.
Hadley, Robert W., & W. J. Lederer.
Department of Pharmacology, College of Medicine, University of
Kentucky, MS-372 UKMC, Lexington, KY 40536, and Department of
Physiology, School of Medicine, University of Maryland, 655 West
Baltimore Street, Baltimore, MD 21201, U.S.A.
APStracts 2:0247H, 1995.
L-type Ca2+ channels were studied in guinea-pig ventricular myocytes,
by examining how photoinactivation of nifedipine affected the Ca2+
current (Ica) and the Ca2+ channel gating current (Ig). Ica, blocked
by nifedipine, reappeared in qualitatively different phases
(immediate and delayed) following photoinactivation of nifedipine.
Immediate recovery was attributed to unblock of closed Ca2+ channels,
while delayed recovery was attributed to unblock of inactivated
channels. In contrast to the Ica results, photoinactivation of
nifedipine produced only delayed recovery of Ig. Analysis of these
results suggests the following conclusions. First, the actions of
inhibitory dihydropyridines can be attributed to binding to either
the inactivated or the closed conformation, but only binding to the
inactivated state is associated with reduction of Ig. Second, the
action of inhibitory dihydropyridines on closed channels is to retard
their movement through a final, voltage-independent transition to the
open state. This effect seems to be the converse of a major action of
stimulatory dihydropyridines, and thus is the principal mechanistic
difference between stimulatory and inhibitory dihydropyridines.
Received 8 February 1995; accepted in final form 6 June 1995.
APS Manuscript Number H116-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.