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dc.contributor.authorElies, Jacobo*
dc.contributor.authorScragg, J.L.*
dc.contributor.authorHuang, S.*
dc.contributor.authorDallas, M.L.*
dc.contributor.authorHuang, D.*
dc.contributor.authorMacDougall, D.*
dc.contributor.authorBoyle, J.P.*
dc.contributor.authorGamper, N.*
dc.contributor.authorPeers, C.*
dc.date.accessioned2017-06-14T14:22:04Z
dc.date.available2017-06-14T14:22:04Z
dc.date.issued2014-12
dc.identifier.citationElies J, Scragg JL, Huang S et al (2014) Hydrogen sulfide inhibits Cav3.2 T-type Ca2 channels. The FASEB Journal. 28(12): 5376-5387.en_US
dc.identifier.urihttp://hdl.handle.net/10454/12207
dc.descriptionNoen_US
dc.description.abstractThe importance of H2S as a physiological signaling molecule continues to develop, and ion channels are emerging as a major family of target proteins through which H2S exerts many actions. The purpose of the present study was to investigate its effects on T-type Ca2+ channels. Using patch-clamp electrophysiology, we demonstrate that the H2S donor, NaHS (10 μM−1 mM) selectively inhibits Cav3.2 T-type channels heterologously expressed in HEK293 cells, whereas Cav3.1 and Cav3.3 channels were unaffected. The sensitivity of Cav3.2 channels to H2S required the presence of the redox-sensitive extracellular residue H191, which is also required for tonic binding of Zn2+ to this channel. Chelation of Zn2+ with N,N,N′,N′-tetra-2-picolylethylenediamine prevented channel inhibition by H2S and also reversed H2S inhibition when applied after H2S exposure, suggesting that H2S may act via increasing the affinity of the channel for extracellular Zn2+ binding. Inhibition of native T-type channels in 3 cell lines correlated with expression of Cav3.2 and not Cav3.1 channels. Notably, H2S also inhibited native T-type (primarily Cav3.2) channels in sensory dorsal root ganglion neurons. Our data demonstrate a novel target for H2S regulation, the T-type Ca2+ channel Cav3.2, and suggest that such modulation cannot account for the pronociceptive effects of this gasotransmitter.en_US
dc.description.sponsorshipThis work was supported by the British Heart Foundation, the Medical Research Council, and the Hebei Medical Universityen_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1096/fj.14-257113en_US
dc.subjectHydrogen sulfide; Ion channels; T-type Ca2 channels; Gasotransmitter; Inhibitsen_US
dc.titleHydrogen sulfide inhibits Cav3.2 T-type Ca2 channelsen_US
dc.status.refereedYesen_US
dc.date.Accepted2014-08-18
dc.date.application2014-09-02
dc.typeArticleen_US
dc.type.versionNo full-text in the repositoryen_US


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