Effects of resibufogenin on voltage-gated sodium channels in cultured rat hippocampal neurons

Voltage-gated sodium channels (VGSCs) play important roles in maintaining the excitability of hippocampal neurons. The present study investigated the effects of resibufogenin (RBG, a main component of bufadienolides) on voltage-gated sodium channel currents (INa) in rat hippocampal neurons using whole-cell patch clamp recording. According to the results, RBG activated INa in a concentration-dependent manner. RBG at 1 μM concentration could alter some channel kinetics of INa, such as activation thresholds, steady-state activation and inactivation curves, time constant of recovery, and activity-dependent attenuation of INa. RBG influenced peak amplitude, overshoot and half-width of the evoked single action potential, and simultaneously lessened the firing rate of evoked repetitive firing. These findings suggested that INa is probably a target of RBG, which may explain the mechanisms for the pathological effects of RBG on central nervous system.

► Resibufogenin activated INa in cultured rat hippocampal neurons. ► Resibufogenin caused inconsistent results in kinetic properties of sodium channels. ► Resibufogenin had complex and diverse targeting sites in sodium channels. ► Resibufogenin influenced multiple properties on action potential.