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The AMP‐activated protein kinase modulates hypothermia‐induced J wave
Author(s) -
Wu ChengI,
Lu YenYu,
Chen, YaoChang,
Lin FengZhi,
Huang JenHung,
Lin YungKuo,
Higa Satoshi,
Chan ChaoShun,
Liu ChihMin,
Chen ShihAnn,
Chen YiJen
Publication year - 2020
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.13247
Subject(s) - ampk , glibenclamide , medicine , activator (genetics) , protein kinase a , endocrinology , chemistry , inward rectifier potassium ion channel , potassium channel , amp activated protein kinase , phosphorylation , biochemistry , ion channel , receptor , diabetes mellitus
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.