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Micro-RNA 133a-3p induces repolarization abnormalities in atrial myocardium and modulates ventricular

Vladislav S Kuzmin1, Alexandra D Ivanova2, Tatiana S Filatova1

  • 1Department of Human and Animal Physiology, Lomonosov Moscow State University, Leninskiye Gory, 1, 12, Moscow, Russia; Department of Physiology, Pirogov Russian National Research Medical University, Moscow, Russia; Laboratory of Cardiac Electrophysiology, National Medical Research Cardiological Complex (NMRCC), Institute of Experimental Cardiology, Moscow, Russia.

European Journal of Pharmacology
|July 26, 2021
PubMed

Insights

MicroRNA-133a-3p, abundant in the heart, influences cardiac electrophysiology by altering ionic currents. This study reveals its role in repolarization abnormalities and QT prolongation, mediated by targeting protein phosphatase 2 and KChIP2.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Cardiology
  • MicroRNA Research

Background:

  • MicroRNA-133a-3p is the most abundant microRNA in the heart.
  • Its precise role in cardiac electrophysiology remains incompletely understood.
  • Understanding microRNA impact is crucial for cardiac function research.

Purpose of the Study:

  • To investigate the effects of microRNA-133a-3p on key ionic currents.
  • To clarify its role in action potential generation and cardiac electrical activity.
  • To elucidate mechanisms underlying its influence on heart electrophysiology.

Main Methods:

  • In vivo and in vitro transfection of rats with microRNA-133a-3p.
  • Conventional electrocardiography (ECG), sharp microelectrode recordings, and patch-clamp techniques.
  • Bioinformatic analysis to identify potential microRNA targets.

Main Results:

  • MicroRNA-133a-3p did not alter sinoatrial node automaticity or basal heart rate.
  • It induced repolarization abnormalities in atrial cardiomyocytes, increasing L-type calcium current (ICa,L).
  • Ventricular cardiomyocytes showed altered ICa,L and transient outward current (Ito), leading to QT prolongation.

Conclusions:

  • MicroRNA-133a-3p accumulation causes chamber-specific electrophysiological changes in the heart.
  • It enhances ICa,L and attenuates Ito, potentially by suppressing protein phosphatase 2 (PPP2CA) and KChIP2.
  • These findings highlight microRNA-133a-3p as a modulator of cardiac electrical activity and repolarization.
Keywords:
Action potentialsAdrenergic signalingArrhythmiaCardiac electrophysiologyCardiomyocytesHeart failureIon currentProtein phosphatasemicroRNAmir-133a-3p

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