Abstract:
: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.
journal_name
J Pharmacol Scijournal_title
Journal of pharmacological sciencesauthors
Horishita T,Ueno S,Yanagihara N,Sudo Y,Uezono Y,Okura D,Sata Tdoi
10.1254/jphs.12106scsubject
Has Abstractpub_date
2012-01-01 00:00:00pages
54-8issue
1eissn
1347-8613issn
1347-8648pii
DN/JST.JSTAGE/jphs/12106SCjournal_volume
120pub_type
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