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Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes
11:33

Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes

Published on: March 12, 2013

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The cardiomyocyte molecular clock regulates the circadian expression of Kcnh2 and contributes to ventricular

Elizabeth A Schroder1, Don E Burgess1, Xiping Zhang1

  • 1Center for Muscle Biology, Department of Physiology.

Heart Rhythm
|February 22, 2015
PubMed

Insights

The heart's molecular clock regulates potassium channel gene expression, impacting ventricular repolarization. Disrupting the cardiomyocyte circadian clock may increase the risk of arrhythmias and sudden cardiac death.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Chronobiology

Background:

  • Sudden cardiac death (SCD) exhibits diurnal variation, potentially linked to circadian regulation of cardiac electrical properties.
  • The basic helix-loop-helix transcription factors BMAL1 and CLOCK are key regulators of circadian gene expression.

Purpose of the Study:

  • To investigate if Bmal1 in cardiomyocytes influences K(+) channel expression and diurnal ventricular repolarization.
  • To determine the role of cardiomyocyte-specific Bmal1 in cardiac electrophysiology.

Main Methods:

  • Utilized inducible cardiomyocyte-specific Bmal1 deletion in transgenic mice (iCSΔBmal1(-/-)).
  • Employed quantitative PCR, voltage clamping, promoter-reporter assays, and electrocardiographic telemetry.

Main Results:

  • Deletion of Bmal1 disrupted the circadian expression of Kcnh2, a K(+) channel gene.
  • Reduced rapidly activating delayed-rectifier K(+) current in iCSΔBmal1(-/-) cardiomyocytes.
  • BMAL1 and CLOCK coexpression transactivated the Kcnh2 promoter.
  • iCSΔBmal1(-/-) mice showed prolonged QT intervals during the light phase.

Conclusions:

  • The cardiac molecular clock regulates Kcnh2 circadian expression and K(+) channel function.
  • Disruption of the cardiomyocyte circadian clock affects ventricular repolarization, potentially increasing arrhythmia risk.
  • Circadian clock mechanisms are crucial for maintaining normal cardiac electrical stability.
Abstract

Keywords:
Bmal1Circadian rhythmECGKcnh2QTcRepolarization

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