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
+/Ca
2+ 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
INa.L in normoxia, concentration-dependently attenuated the increase of
INa.L, which thereby decreased the reverse
INCX, and obviously relieved EADs during hypoxia.
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