Multilayer control of cardiac electrophysiology by microRNAs

The electrophysiological properties of the heart include cardiac automaticity, excitation (i.e., depolarization and repolarization of action potential) of individual cardiomyocytes, and highly coordinated electrical propagation through the whole heart. An abnormality in any of these properties can cause arrhythmias. MicroRNAs (miRs) have been recognized as essential regulators of gene expression through the conventional RNA interference (RNAi) mechanism and are involved in a variety of biological events. Recent evidence has demonstrated that miRs regulate the electrophysiology of the heart through fine regulation by the conventional RNAi mechanism of the expression of ion channels, transporters, intracellular Ca²⁺-handling proteins, and other relevant factors. Recently, a direct interaction between miRs and ion channels has also been reported in the heart, revealing a biophysical modulation by miRs of cardiac electrophysiology. These advanced discoveries suggest that miR controls cardiac electrophysiology through two distinct mechanisms: immediate action through biophysical modulation and long-term conventional RNAi regulation. Here, we review the recent research progress and summarize the current understanding of how miR manipulates the function of ion channels to maintain the homeostasis of cardiac electrophysiology.