Ranolazine Attenuates the Enhanced Reverse Na⁺-Ca²⁺ Exchange Current via Inhibiting Hypoxia-Increased Late Sodium Current in Ventricular Myocytes

抄録

Ranolazine (RAN), a novel antianginal agent, inhibits the increased late sodium current (I_Na.L) under many pathological conditions. In this study, the whole-cell patch-clamp technique was used to explore the effects of RAN on I_Na.L and reverse Na⁺/Ca²⁺ exchange current (I_NCX) in rabbit ventricular myocytes during hypoxia. Tetrodotoxin (TTX) at 2 μM or RAN at 9 μM decreased significantly I_Na.L and reverse I_NCX 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 I_Na.L and reverse I_NCX in a concentration-dependent manner. Hypoxia-increased I_Na.L and reverse I_NCX 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 I_NCX by inhibiting I_Na.L in normoxia, concentration-dependently attenuated the increase of I_Na.L, which thereby decreased the reverse I_NCX, and obviously relieved EADs during hypoxia.