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XB-ART-45782
J Pharmacol Sci 2012 Jan 01;1201:54-8. doi: 10.1254/jphs.12106sc.
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Inhibition by pregnenolone sulphate, a metabolite of the neurosteroid pregnenolone, of voltage-gated sodium channels expressed in Xenopus oocytes.

Horishita T, Ueno S, Yanagihara N, Sudo Y, Uezono Y, Okura D, Sata T.


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Neurosteroids are known as allosteric modulators of the ligand-gated ion channel superfamily. Voltage-gated sodium channels (Na(v)) play an important role in mediating excitotoxic damages. Here we report the effects of neurosteroids on the function of Na(v), using voltage-clamp techniques in Xenopus oocytes expressed with the Na(v)1.2 α subunit. Pregnenolone sulphate, but not pregnenolone, inhibited sodium currents (I(Na)) at 3 - 100 μmol/L. The suppression of I(Na) 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 Na(v) via increased inactivation, which may contribute to the neuroprotection.

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