Inhibition by pregnenolone sulphate, a metabolite of the neurosteroid pregnenolone, of voltage-gated sodium channels expressed in Xenopus oocytes

Abstract

Neurosteroids are known as allosteric modulators of the ligand-gated ion channel superfamily. Voltage-gated sodium channels (Nav) play an important role in mediating excitotoxic damages. Here we report the effects of neurosteroids on the function of Nav, using voltage-clamp techniques in Xenopus oocytes expressed with the Nav1.2 α subunit. Pregnenolone sulphate, but not pregnenolone, inhibited sodium currents (I Na) at 3 - 100 μmol/L. The suppression of INa by pregnenolone sulphate was due to increased inactivation with little change in activation. These findings suggest that pregnenolone sulphate, a metabolite of pregnenolone, suppresses the function of Nav via increased inactivation, which may contribute to the neuroprotection. © The Japanese Pharmacological Society.