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

Abstract

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 30℃ and 37℃ before and after administration of 4-aminopyridine (an ultrarapid delayed rectifier potassium current inhibitor, I_Kur , 50 µmol L^-1 ), PF06409577 (an AMPK activator, 1 µmol L^-1 ), compound C (an AMPK inhibitor, 10 µmol L^-1 ) and glibenclamide (an ATP-sensitive inward rectifier potassium channel inhibitor, I_KATP , 20 µmol L^-1 ).

Results: The amplitude of the J wave (2.46 ± 0.34 mV vs. 1.11 ± 0.23 mV, P < .01) at 30℃ (n = 15) was larger than that at 37℃ (n = 15). PF06409577 (1 µmol L^-1 ) increased the J waves at both 30℃ and 37℃. In contrast, compound C (10 µmol L^-1 ) reduced J wave at both 37℃ and 30℃. Low-temperature-induced J waves were individually suppressed by 4-AP (50 µmol L^-1 ) and glibenclamide (20 µmol L^-1 ).

Conclusions: AMPK inhibition reduces low-temperature-induced J waves and possible ventricular arrhythmogenesis by modulating I_KATP and I_Kur channels.

Keywords: AMPK; Hypothermia; J wave; Langendorff; Ventricular arrhythmia.