Electrophysiological effects of L-palmitoylcarnitine in single ventricular myocytes.
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.
Mészàros
J
J
Department of Pharmacology, University of Connecticut Health Center, Farmington 06032.
Pappano
A J
AJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives*; D002469:Cell Separation; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009439:Neuraminidase / Q000494:pharmacology; D009994:Osmolar Concentration; D010172:Palmitoylcarnitine / Q000494:pharmacology*; D012433:Ryanodine / Q000494:pharmacology; D013997:Time Factors
D012433:Ryanodine; D010172:Palmitoylcarnitine; D009439:Neuraminidase; D002331:Carnitine; D002118:Calcium