AJP - Heart and Circulatory Physiology, Vol 258, Issue 4 931-H938, Copyright © 1990 by American Physiological Society
Electrophysiological effects of L-palmitoylcarnitine in single ventricular myocytes
J. Meszaros and A. J. Pappano
Department of Pharmacology, University of Connecticut Health Center, Farmington 06032.
In isolated guinea pig ventricular myocytes, L-palmitoylcarnitine (L-PC)
produced concentration- and time-dependent changes of resting potential
(RP) and action potential duration at 50% repolarization (APD50). At 10(-8)
to 10(-6) M, L-PC increased APD50 without changing RP. At 10(-5) M, the
amphiphile initially increased (0-10 min) and eventually decreased (greater
than 10 min) APD50; the membrane depolarized when APD50 decreased.
Additionally, transient depolarizations (TDs) were consistently induced in
10(-5) M L-PC within 10 min, and TD amplitude progressively increased with
continued exposure to L-PC. The TDs induced in L-PC were augmented by
membrane depolarization, elevated extracellular Ca2+ concentration
([Ca2+]o), and increased number of stimuli. Elevated [Ca2+]o or
neuraminidase treatment also allowed TDs. In neuraminidase, the changes of
RP, APD50, and TD amplitude were qualitatively similar to those seen with
L-PC. These results are consistent with the hypothesis that 10(-5) M L-PC
causes intracellular Ca2+ overload. The blockade of L-PC and
neuraminidase-induced TDs by ryanodine is consistent with the intracellular
Ca2+ overload hypothesis.
