Ranolazine attenuates stretch-induced modifications of electrophysiological characteristics in HL-1 cells

Mechanical stretch induces an increase in Na+ influx into myocytes, related to mechanisms including stretch-activated channels or activation of Na+/H+ exchanger, involving changes in electrophysiological properties favouring arrhythmia induction. The aim of this study is to investigate the effects of mechanical stretch in cultured atrial murine cells (HL-1 myocytes) and its pharmacological response to ranolazine. Confluent HL-1 myocytes with spontaneous fibrillatory activity was cultured in silicone membrane plates, and were stretched to 110% of resting length. The response to stretch under control conditions and under ranolazine effects was analyzed using a high-resolution optical mapping system. HL-1 cells stretching increased atrial fibrillation dominant frequency in control conditions. The administration of ranolazine reduced this stretch-induced effect, and slowed the arrhythmia in baseline conditions. Ranolazine attenuates the modifications of electrophysiological effects induced by myocardial stretch in HL-1 cells model of AF.