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

Cheng I. Wu, Yen Yu Lu, Yao Chang Chen, Feng Zhi Lin, Jen Hung Huang, Yung Kuo Lin, Satoshi Higa, Chao Shun Chan, Chih Min Liu, Shih Ann Chen, Yi Jen Chen

Research output: Contribution to journalArticlepeer-review

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, IKur, 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, IKATP, 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 IKATP and IKur channels.

Original languageEnglish
Article numbere13247
JournalEuropean Journal of Clinical Investigation
Volume50
Issue number6
DOIs
Publication statusPublished - Jun 1 2020

Keywords

  • AMPK
  • Hypothermia
  • J wave
  • Langendorff
  • Ventricular arrhythmia

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry

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