Lysophosphatidylcholine decreases single channel conductance of inward rectifier K channel in mammalian ventricular myocytes.

Abstract

Summary Effect of lysophosphatidylcholine (LPC) on the inward rectifier K channel of the isolated guinea pig ventricular cell was studied using patch clamp technique. In that LPC (100 ,uM) decreased the magnitude of the single channel conductance from 48±5 pS (mean and S.D., n=5) to 12±9 pS (n=8), this event may be the prime factor related to the alleged LPC-induced depolarization of cardiac tissues.

Effects of lysophosphatidylcholine on electrophysiological properties and excitation-contraction coupling in isolated guinea pig ventricular myocytes.

“…Once the rapid phase of membrane depolarization occurred the effects of LPC were irreversible. Qualitatively similar results were obtained in four myocytes exposed to 20 AtM LPC at 350C, as illustrated in the lower panels of Fig. 3.…”

“…In intact ventricular muscle and Purkinje fibers, electrophysiological effects of lysophosphoglycerides include decreases in diastolic resting potential, action potential amplitude and duration, and the appearance of abnormal automaticity, delayed afterdepolarizations, and triggered activity (13)(14)(15)(16)(17)(18). Similar effects have been described in single ventricular myocytes (19,20). Many of these effects are suggestive of intracellular Ca2+ overload, and Sedlis et al (21,22) showed that lysophosphoglycerides induced an increase in total intracellular Ca2" measured with 45Ca2+.…”

“…Which of these effects predominates, however, depends critically on concentration, temperature, and other experimental factors. Previous studies in cardiac muscle have found that LPC concentrations of 10-75 gM are sufficient to produce electrophysiological derangements in multicellular (13)(14)(15)(16)(17)(18) and isolated myocyte preparations (19,20) studied at room temperature or 37°C. These concentrations are comparable to the reported critical micelle concentration, which may range from 7 to 80 ,M (40,41).…”

“…The inward rectifier K+ current (IKI), the major determinant of resting membrane potential in heart muscle, has previously been reported to be depressed byXLPC (14,19,20). Fig.…”

“…They also found an increase in twitch tension which they could not account for. In single guinea pig ventricular myocytes studied with the patch clamp technique, Kiyosue et al (19,20) demonstrated a decrease in both the macroscopic and unitary currents through inward rectifier K+ channels, although there was no change in the L-type Ca2+ current. In isolated membrane patches from guinea pig ventricular myocytes the lysophosphoglyceride lysophosphatidylcholine (LPC)' altered Na+ channel inactivation (23) and suppressed ATP-sensitive K+ channels (24).…”