Ranolazine inhibits hypoxia‐stimulated late sodium current

Suppression of re-entrant and multifocal ventricular fibrillation by the late sodium current blocker ranolazine.

OBJECTIVES The purpose of this study was to test the hypothesis that the late Na current blocker ranolazine suppresses re-entrant and multifocal ventricular fibrillation (VF). BACKGROUND VF can be caused by either re-entrant or focal mechanism. METHODS Simultaneous voltage and intracellular Ca(+)² optical mapping of the left ventricular epicardial surface along with microelectrode recording...

Reversal by ranolazine of doxorubicin-induced prolongation in the inactivation of late sodium current in rat dorsal root ganglion neurons.

Ranolazine antagonizes the effects of increased late sodium current on intracellular calcium cycling in rat isolated intact heart.

Pathological conditions, including ischemia and heart failure, are associated with altered sodium channel function and increased late sodium current (I(Na,L)), leading to prolonged action potential duration, increased intracellular sodium and calcium concentrations, and arrhythmias. We used anemone toxin (ATX)-II to study the effects of increasing I(Na,L) on intracellular calcium cycling in rat...

An emerging antiarrhythmic target: late sodium current.

The cardiac late sodium current (INa,L) has been in the focus of research in the recent decade. The first reports on the sustained component of voltage activated sodium current date back to the seventies, but early studies interpreted this tiny current as a product of a few channels that fail to inactivate, having neither physiologic nor pathologic implications. Recently, the cardiac INa,L has ...

Late sodium current inhibition alone with ranolazine is sufficient to reduce ischemia- and cardiac glycoside-induced calcium overload and contractile dysfunction mediated by reverse-mode sodium/calcium exchange.

Excessive reverse-mode (RM) sodium/calcium exchanger 1.1 (NCX1.1) activity, resulting from intracellular sodium accumulation caused by reduced Na+/K+-ATPase activity, increased Na-H exchanger 1 activity. The induction of the voltage-gated sodium channel late current component (late INa), is a major pathway for intracellular calcium (Ca2+i) loading in cardiac ischemia-reperfusion (IR) injury and...