Pregnenolone Sulfate Potentiates the Inwardly Rectifying K+ Channel Kir2.3 英文参考文献.docVIP

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Pregnenolone Sulfate Potentiates the Inwardly Rectifying K+ Channel Kir2.3 英文参考文献.doc

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PregnenoloneSulfatePotentiatestheInwardlyRectifyingKChannelKir2.3英文参考文献

PregnenoloneSulfatePotentiatestheInwardly RectifyingK ChannelKir2.3 + ToruKobayashi1*,KazuoWashiyama1,KazutakaIkeda2 1DepartmentofMolecularNeuropathology,BrainResearchInstitute,NiigataUniversity,Chuo-ku,Niigata,Niigata,Japan,2DivisionofPsychobiology,TokyoInstituteof Psychiatry,Setagaya,Tokyo,Japan Abstract Background: Neurosteroids have various physiological and neuropsychopharmacological effects. In addition to the genomic effects of steroids, some neurosteroids modulate several neurotransmitter receptors and channels, such as N- 2+ methyl-D-aspartatereceptors,c-aminobutyricacidtypeA(GABAA)receptors,ands1receptors,andvoltage-gatedCa and channels. However, the molecular mechanisms underlying the various effects of neurosteroids have not yet been + K sufficientlyclarified.Inthenervoussystem,inwardlyrectifyingK (Kir)channelsalsoplayimportantrolesinthecontrolof restingmembranepotential,cellularexcitabilityandK homeostasis.AmongconstitutivelyactiveKir2channelsinamajor Kir subfamily, Kir2.3 channels are expressed predominantly in the forebrain, a brain area related to cognition, memory, emotion,andneuropsychiatricdisorders. + + Methodology/PrincipalFindings:ThepresentstudyexaminedtheeffectsofvariousneurosteroidsonKir2.3channelsusing theXenopusoocyteexpressionassay.InoocytesinjectedwithKir2.3mRNA,onlypregnenolonesulfate(PREGS),amongnine neurosteroids tested, reversibly potentiated Kir2.3 currents. The potentiation effect was concentration-dependent in the micromolar range, and the current-voltage relationship showed inward rectification. However, the potentiation effect of PREGS was not observed when PREGS was applied intracellularly and was not affected by extracellular pH conditions. Furthermore, although Kir1.1, Kir2.1, Kir2.2, and Kir3 channels were insensitive to PREGS, in oocytes injected with Kir2.1/ Kir2.3orKir2.2/Kir2.3mRNA,butnotKir2.1/Kir2.2mRNA,PREGSpotentiatedKircurrents.Thesepotentiationpropertiesin theconcentration-responserelationshipswerelesspot