Lipotransfection of miR-1-3p, miR-133a-3p and miR-153-3p changes the electrophysiological characteristics of rat working myocardium

Abstract

MicroRNAs (miR) are small single-stranded ribonucleotide sequences, which regulate gene expression at the post-transcriptional level. It has been shown that some miRs play a key role in cardiovascular physiology and pathophysiology. In this work the effects of lipotransfection of miR-1-3p, miR-133a-3p and miR-153-3p on electrophysiological parameters of myocardial tissue were studied for the first time. Action potentials (AP) were recorded in multicellular Tyrode-perfused rat atria preparations after the injection of transfection mixture consisting of lipofectamine and miR-1-3p, miR-133a-3p or miR-153-3p with the usage of microelectrode technique. It was shown that treatment of myocardial tissue with transfection mixture itself leads to a prolongation of AP repolarization phase. Herewith, miR-1-3p, miR-153-3p did not cause a significant change in AP configuration within 6 hrs after the injection in tissue preparations compared to the injection of transfection mixture free of miRs. At the same time, miR-133a-3p caused a significant increase in AP duration at the level of 90% repolarization and the effect was maximal 4 hrs after transfection. Based on the bioinformatic search and analysis of possible miR-133a-3p targets, it was suggested that this miR can interact with the mRNA of a number of protein phosphatases. A suppression of protein phosphatase expression in cardiomyocytes may underlie the observed increase in AP duration under the action of miR-133a-3p due to the affection of proteins involved in calcium dynamics.