Inhibitory effects of palmitoylcarnitine and lysophosphatidylcholine on the sodium current of cardiac ventricular cells.
We investigated the effects of ischemia-related amphipathic compounds, palmitoylcarnitine (PamCar, 0.5-50 microM) and lysophosphatidylcholine (lysoPtdCho, 5-50 microM) on sodium current (INa) of guinea-pig ventricular myocytes. The cells were perfused with low-Na+ (60 mM) Tyrode's solution, and Ca2+ and K+ currents were blocked by external Co2+ (3 mM) and internal Cs+ (140 mM), respectively. INa was elicited by depolarizing voltage steps from a holding potential of -100 mV at a temperature of 33 degrees C. PamCar (5 microM) decreased the peak INa (attained at -20 mV or -30 mV) from 6.1 +/- 2.1 nA to 3.9 +/- 1.4 nA (n = 11), or by 36.1% within 2 min, and shifted the curve of steady-state INa inactivation by 5.4 mV in the positive direction (from -76.3 +/- 4.6 mV, control to -70.9 +/- 4.0 mV, in PamCar, n = 4). Partial restoration of the amplitude and the shift of the steady-state inactivation curve of INa was attained after washout of PamCar. In contrast, lysoPtdCho at concentrations over 10 microM irreversibly depressed the INa within 0.5-3 min and the reduction of INa was followed by cell contracture or cell death (n = 9). The survival time, defined as a period from the start of lysoPtdCho application to the time of the last successful recording of the INa (before evolution of sudden changes in the holding current), depended on the concentrations of lysoPtdCho. Both PamCar and lysoPtdCho retarded the time course of activation and inactivation of INa.(ABSTRACT TRUNCATED AT 250 WORDS)
Sato
T
T
Department of Physiology, Medical College of Oita, Japan.
Kiyosue
T
T
Arita
M
M
D000818:Animals; D004594:Electrophysiology; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology; D010172:Palmitoylcarnitine / Q000494:pharmacology*; D012964:Sodium / Q000502:physiology*
D008244:Lysophosphatidylcholines; D010172:Palmitoylcarnitine; D012964:Sodium