Abstract
Cardiac arrhythmias are prevalent among humans across all age ranges, affecting millions of people worldwide. While cardiac arrhythmias vary widely in their clinical presentation, they possess shared complex electrophysiologic properties at cellular level that have not been fully studied. Over the last decade, our current understanding of the functional roles of non-coding RNAs have progressively increased. microRNAs represent the most studied type of small ncRNAs and it has been demonstrated that miRNAs play essential roles in multiple biological contexts, including normal development and diseases. In this review, we provide a comprehensive analysis of the functional contribution of non-coding RNAs, primarily microRNAs, to the normal configuration of the cardiac action potential, as well as their association to distinct types of arrhythmogenic cardiac diseases.
Highlights
Role of ncRNAs in the Cardiac Action PotentialThe upstroke phase of the cardiac action potential in fast conducting cells, i.e., atrial and ventricular myocytes, is primarily modulated by the fast INa current (NaV 1.5) with a smaller contribution of Nav 1.8
Cardiac arrhythmias are prevalent among humans across all age ranges, affecting millions of people worldwide
While emerging evidence is progressively increasing on the functional role of microRNAs on the regulation of SCN5A/NaV 1.5, to date no information is available upon their putative contribution to sodium channel ancillary subunits in the cardiovascular contexts, some reports for miR-449a, miR-34a, miR-133b, miR-143-3p, and miR1-3p modulating SCN2B/NaV β2 [54,55,56,57], miR-375 modulating SCN3B/NaV β3 [58], and miR-3175 and miR-424-5p modulating SCN4B/NaV β4 [59,60] have been described in other biological contexts
Summary
The upstroke phase of the cardiac action potential in fast conducting cells, i.e., atrial and ventricular myocytes, is primarily modulated by the fast INa current (NaV 1.5) with a smaller contribution of Nav 1.8. While emerging evidence is progressively increasing on the functional role of microRNAs on the regulation of SCN5A/NaV 1.5, to date no information is available upon their putative contribution to sodium channel ancillary subunits in the cardiovascular contexts, some reports for miR-449a, miR-34a, miR-133b, miR-143-3p, and miR1-3p modulating SCN2B/NaV β2 [54,55,56,57], miR-375 modulating SCN3B/NaV β3 [58], and miR-3175 and miR-424-5p modulating SCN4B/NaV β4 [59,60] have been described in other biological contexts. Distinct microRNAs such as miR-1 [136], let-7a [137], miR-625-5p [138], miR-525-5p [139], miR-338-5p [140], miR-185 [141], miR-145 [142], miR-30b-5p [143], and miR-675 [144] have been reported to modulate calmodulin expression, these reports exclusively describe their functional role in cardiac hypertrophy and failed to provide a direct link to sodium channel regulation. Nedd ubiquitin ligases role in Nav 1.5 have been reported [150,151,152]. miR-1 targets Nedd in Drosophila and Nedd4l in mammals, supporting a plausible role modulated trafficking or degrading Need4/Need4l substrates in the heart—such as Scn5a [153]—yet direct evidence remains to be elucidated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
