Inhibitory effects of neferine on Nav1.5 channels expressed in HEK293 cells

Abstract

Neferine, a bisbenzylisoquinoline alkaloid in Lotus Plumule, was proved to have a wide range of biological activities. In the present study, using whole-cell patch-clamp technique, we investigated the effects of neferine on Na_v1.5 channels that are stably expressed in HEK 293 cells. We found that neferine potently and reversibly inhibited Na_v1.5 currents in a concentration dependent manner with a half-maximal inhibition (IC₅₀) being 26.15 μmol/L. The inhibitory effects of neferine on Na_v1.5 currents were weaker than those of quinidine at the same concentration. The steady-state inactivation curve was significantly shifted towards hyperpolarizing direction in the presence of 30 μmol/L neferine, while the voltage-dependent activation was unaltered. Neferine prolonged the time to peak of activation, increased the inactivation time constants of Na_v1.5 currents and markedly slowed the recovery from inactivation. The inhibitory effect of neferine could be potentiated in a frequency-dependent manner. These results suggested that neferine can block Na_v1.5 channels under the open state and inactivating state and it is an open channel blocker of Na_v1.5 channels.

Keywords

neferine / Na_v1.5 channel / whole-cell patch-clamp / HEK293 cells

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