Ranolazine attenuates the enhanced reverse Na+-Ca2+ exchange current via inhibiting hypoxia-increased late sodium current in ventricular myocytes

Ranolazine (ran),a novel antianginal agent,inhibits the increased late sodium current (ina.l) under many pathological conditions. in this study,the whole-cell patch-clamp technique was used to explore the effects of ran on ina.l and reverse na+/ca2+ exchange current (incx) in rabbit ventricular myocytes during hypoxia. tetrodotoxin (ttx) at 2 μm or ran at 9 μm decreased significantly ina.l and reverse incx under normoxia and ran had no further effects on both currents in the presence of ttx. ran (3,6,and 9 μm) attenuated hypoxia-increased ina.l and reverse incx in a concentration-dependent manner. hypoxia-increased ina.l and reverse incx were inhibited by 2 μm ttx,whereas 9 μm ran applied sequentially did not further decrease both currents. in another group,after both currents were decreased by 9 μm ran,2 μm ttx had no further effects in the presence of ran. in monophasic action potential (map) recording,early after-depolarizations (eads) were suppressed by ran (9 μm) during hypoxia. in conclusion,ran decreased reverse incx by inhibiting i na.l in normoxia,concentration-dependently attenuated the increase of ina.l,which thereby decreased the reverse incx,and obviously relieved eads during hypoxia. © the japanese pharmacological society.