Ranolazine inhibits shear sensitivity of endogenous Na+ current and spontaneous action potentials in HL-1 cells.

摘要: NaV1.5 is a mechanosensitive voltage-gated Na+ channel encoded by the gene SCN5A, expressed in cardiac myocytes and required for phase 0 of action potential (AP). In cardiomyocyte, ranolazine inhibits depolarizing current delayed rectifier (IKr) currents. Recently, was also shown to be an inhibitor mechanosensitivity. Stretch accelerates firing frequency SA node, fluid shear stress increases beating rate cultured cardiomyocytes vitro. However, no cell platform exists currently examination spontaneous electrical activity response mechanical stimulation. present study, flow solution over atrial myocyte-derived HL-1 cells used study mechanosensitivity spontaneous, endogenous rhythmic potentials. voltage-clamped cells, bath increased peak 14 ± 5%. current-clamped decay AP 27 12% 18 4%, respectively. Ranolazine blocked both responses stress. This suggests that are viable vitro model detailed effects stimulation on Inhibition potentials mechanisms behind antiarrhythmic effect ranolazine.