Lysophosphatidylcholine, a putative biochemical mediator of ischemia-induced arrhythmias, reduces the resting potential of ventricular muscle. To elucidate possible mechanisms of lysophosphatidylcholine-induced depolarization, we investigated the effects of lysophosphatidylcholine on the electrophysiological properties of cat ventricular muscle, using potassium ion-selective electrodes and conventional microelectrode, current-, and voltage-clamp techniques. Lysophosphatidylcholine (50 microM) decreased the sensitivity of the resting potential to changes in extracellular potassium concentration. Hyperpolarization of lysophosphatidylcholine-depolarized fibers by current-clamp methods failed to reveal two stable levels of resting potential. Depolarizing concentrations of lysophosphatidylcholine did not reduce the potassium equilibrium potential, as determined from the reversal potential of the time-dependent potassium current and measurements of intracellular potassium activity using potassium ion-selective electrodes. Lysophosphatidylcholine induced a depolarizing shift of the reversal potential for steady state current, and did not induce the formation of a negative slope region in the steady state current-voltage or background current-voltage relationships. Lysophosphatidylcholine induced an inward shift and linearization of the background current-voltage relationship negative to -30 mV, and the lysophosphatidylcholine-sensitive component of the background current was an inward rectifier with a reversal potential approximately equal to the potassium equilibrium potential. Lysophosphatidylcholine also reduced the amplitudes of the time-dependent potassium current, slow inward current, and the potassium accumulation and depletion currents. These results indicate that lysophosphatidylcholine-induced depolarization is due, in part, to reduced potassium conductance at voltages near the normal resting potential, and that lysophosphatidylcholine may act as a nonspecific depressant of membrane channels.
- Copyright © 1983 by American Heart Association