Bay k 8644 depresses excitation-contraction coupling in cardiac
muscle.
McCall, E., and D. M. Bers.
Department of Physiology, Loyola University Medical Center, 2160
South First Avenue, Maywood, Illinois 60153
APStracts 2:0349C, 1995.
We determined the effect of the dihydropyridine L-type Ca channel
agonist Bay K 8644 (BAY) on excitation-contraction coupling (E-C
coupling) in isolated ferret ventricular myocytes using whole-cell
voltage clamp. The SR Ca load during the test pulses, assessed by
caffeine-induced contractures (CafC), was similar in the presence and
absence of BAY, with [Ca]o lowered from 3 mM to 1 mM in BAY. The
relationship between L-type Ca current (ICa) and contraction was
assessed, with current and contractions measured during
depolarizations from -40 to between -30 and +50 mV after a
conditioning train (to ensure constant SR Ca load). BAY shifted the
current-contraction relationship downward, such that for a given ICa
and SR Ca load, the contraction elicited was much smaller in the
presence of BAY. BAY also induced a characteristic negative shift in
the current-voltage relationship. We conclude that BAY decreases the
efficacy of a given Ca current to induce SR Ca release during E-C
coupling in ferret cardiac tissue (in contrast to the BAY-induced
increase of resting SR Ca release). This may reflect an alteration in
the state of the SR Ca release channel due to BAY binding to
dihydropyridine receptors.
Received 24 July 1995; accepted in final form 18 September 1995.
APS Manuscript Number C451-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95