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

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.