Effects of Lysophosphatidylcholine on Ion Transporters in the Heart

Abstract

Lysophosphatidylcholine (LPC) is an amphiphilic lipid metabolite that accumulates in ischemic myocardium and plays a role in the genesis of ischemia-induced arrhythmias. In canine Purkinje fibers, LPC (100μM) decreased maximum diastolic potential, action potential amplitude, and action potential durations and induced rhythmic automatic depolarizations from depolarized membrane potentials. The marked membrane depolarization was not associated with a comparable decrease in the intracellular K+ activity as measured by K+-selective microelectrodes. Therefore, the LPC-induced membrane depolarization could be mainly caused by a decrease in background K+ conductance rather than a potassium leak from the intracellular space. In guinea pig papillary muscles, LPC produced slight decreases in the resting membrane potential, action potential amplitude, and action potential duration concomitantly with an increase in twitch tension. The positive inotropic response to LPC was accompanied by an increase in intracellular Na+ activity, which might stem from the inhibition of Na+-K+ ATPase or the activation of nonspecific cation channels by LPC. In quiescent papillary muscles, effects of LPC (30μM) on the intracellular pH (pHi) regulatory system were examined using pH-sensitive microelectrodes. In a CO2/HCO2 −-buffered solution, LPC decreased the pHi recovery rate from an intracellular acid load produced by NH4CI prepulsing. LPC slowed the pHi recovery in the presence of the Na+-H+ antiport blocker 5-(N-N-hexamethylene) amiloride but not in the presence of the Na+-HCO3 − symport blocker 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS, 0.5 mM), suggesting that LPC selectively impairs the Na+-HCO3 − symport. Thus, LPC may potentiate arrhythmogenic action by intensifying intracellular acidosis in ischemic myocardium.