ELECTROPHYSIOLOGICAL EFFECTS OF PALMITATE ON RABBIT PULMONARY VEIN MYOCARDIAL CELLS

摘要

Excess saturated fatty acids such as palmitate could induce action potential (AP) abnormalities and subsequent arrhythmias. The aim of present experiments was to explore the underlying electrophysiological mechanisms. Forty-three cardiac myocytes were isolated enzymatically from rabbit left atrial-pulmonary vein myocardial sleeves (PV), which had been shown to contain ectopic foci. Eleven of them had spontaneous activity (0.69+-0.15 Hz) while the remaining 32 myocytes were driven electrically at a rate of 1 Hz in room temperature (22~25(deg)C). Results of whole-cell patch-clamp studies show that acute exposure (<60 minutes) to palmitate (0.3 mM) suppressed automatic rhythms, shortened AP duration, shifted resting membrane potential (RMP) from -59+-3 to -46+-4 mV and decreased amplitude of delayed afterdepolarization. Ionic currents measurements revealed that palmitate reduced I_(ca,L) and I_(to) on depolarization from a holding potential of -40 mV, and decreased IKi on hyperpolarization. The reduced II_(ca,L) and an enhanced I_k (but not a smaller I_(to)) could explain the shortening in AP duration. The reduced II_(K1) was matched with the fall in RMP and prone to arrhythmias. The present findings indicate that acute exposure to palmitate could induce multiple actions on electrical properties of PV cardiomyocytes which might lead to both arrhythmogenic and antiarrhythmic effects.