The AMP-Activated Protein Kinase Modulates Hypothermia-Induced J Wave.

Background 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. Methods 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 30celcius and 37celcius before and after administration of 4-aminopyridine (an ultrarapid delayed rectifier potassium current inhibitor, I-Kur, 50 mu mol L-1), PF06409577 (an AMPK activator, 1 mu mol L-1), compound C (an AMPK inhibitor, 10 mu mol L-1) and glibenclamide (an ATP-sensitive inward rectifier potassium channel inhibitor, I-KATP, 20 mu mol L-1). Results The amplitude of the J wave (2.46 +/- 0.34 mV vs. 1.11 +/- 0.23 mV, P < .01) at 30celcius (n = 15) was larger than that at 37celcius (n = 15). PF06409577 (1 mu mol L-1) increased the J waves at both 30celcius and 37celcius. In contrast, compound C (10 mu mol L-1) reduced J wave at both 37celcius and 30celcius. Low-temperature-induced J waves were individually suppressed by 4-AP (50 mu mol L-1) and glibenclamide (20 mu mol L-1). Conclusions AMPK inhibition reduces low-temperature-induced J waves and possible ventricular arrhythmogenesis by modulating I-KATP and I-Kur channels.