The AMP-activated protein kinase modulates hypothermia-induced J wave.

Abstract

The mechanism underlying the occurrence of the J wave in low temperature remains unclear. However, low temperature is associated with metabolic disorder and 5' AMP-activated protein kinase (AMPK), which modulates ionic currents and cardiac metabolism. This study investigated whether AMPK regulation can modulate the occurrence of the J wave at low temperature. Unipolar and bipolar leads were used to record monophasic action potential (the endocardium and epicardium) and pseudo-electrocardiograms (inferior leads) to study the cardiac electrical activity. Measurements were taken in isolated Langendorff rabbit hearts at both 30℃ and 37℃ before and after administration of 4-aminopyridine (an ultrarapid delayed rectifier potassium current inhibitor, IKur , 50µmol L-1 ), PF06409577 (an AMPK activator, 1µmol L-1 ), compound C (an AMPK inhibitor, 10µmol L-1 ) and glibenclamide (an ATP-sensitive inward rectifier potassium channel inhibitor, IKATP , 20µmol L-1 ). The amplitude of the J wave (2.46±0.34mV vs. 1.11±0.23mV, P<.01) at 30℃ (n=15) was larger than that at 37℃ (n=15). PF06409577 (1µmol L-1 ) increased the J waves at both 30℃ and 37℃. In contrast, compound C (10µmol L-1 ) reduced J wave at both 37℃ and 30℃. Low-temperature-induced J waves were individually suppressed by 4-AP (50µmol L-1 ) and glibenclamide (20µmol L-1 ). AMPK inhibition reduces low-temperature-induced J waves and possible ventricular arrhythmogenesis by modulating IKATP and IKur channels.