Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
J Pharmacol Sci. 2012;120(1):54-8. doi: 10.1254/jphs.12106sc. Epub 2012 Aug 8.
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.
神经甾体是配体门控离子通道超家族的别构调节剂。电压门控钠离子通道（Na(v)）在介导兴奋性毒性损伤中起重要作用。本文采用 Xenopus oocytes 表达 Na(v)1.2α亚基的电压钳技术，报道了神经甾体对 Na(v)功能的影响。硫酸孕烯醇酮（pregnenolone sulphate）而非孕烯醇酮（pregnenolone）在 3-100 μmol/L 时抑制钠电流（I(Na)）。硫酸孕烯醇酮抑制 I(Na)的作用是由于失活增加，而激活几乎没有变化。这些发现表明，孕烯醇酮的代谢产物硫酸孕烯醇酮通过增加失活来抑制 Na(v)的功能，这可能有助于神经保护。
