Channels
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Evidence supports a role for the tetrodotoxin-sensitive Na(V)1.7 and the tetrodotoxin-resistant Na(V)1.8 in the pathogenesis of pain. Ranolazine, an anti-ischemic drug, has been shown to block cardiac (Na(V)1.5) late sodium current (I(Na)). In this study, whole-cell patch-clamp techniques were used to determine the effects of ranolazine on human Na(V)1.7 (hNa(V)1.7 + beta(1) subunits) and rat Na(V)1.8 (rNa(V)1.8) channels expressed in HEK293 and ND7-23 cells, respectively. ⋯ An increase of depolarizing pulse duration from 3 to 200 msec did not affect the use-dependent block of I(Na) by 100 microM ranolazine. Taken together, the data suggest that ranolazine blocks the open state and may interact with the inactivated states of Na(V)1.7 and Na(V)1.8 channels. The state-and use-dependent modulation of hNa(V)1.7 and rNa(V)1.8 Na+ channels by ranolazine could lead to an increased effect of the drug at high firing frequencies, as in injured neurons.