title: Mechanism of inhibition by hydrogen sulfide of native and recombinant BKCa channels.
abstract: Recent evidence suggests that H(2)S contributes to activation of the carotid body by hypoxia by inhibiting K(+) channels. Here, we determine both the molecular identity of the K(+) channel target within the carotid body and the biophysical characteristics of the H(2)S-evoked inhibition by analyzing native rat and human recombinant BK(Ca) channel activity in voltage-clamped, inside-out membrane patches. Rat glomus cells express the enzymes necessary for the endogenous generation of H(2)S, cystathionine-beta-synthase and cystathionine-gamma-lyase. H(2)S inhibits native carotid body and human recombinant BK(Ca) channels with IC(50) values of around 275 microM. Inhibition by H(2)S is rapid and reversible, works by a mechanism which is distinct from that suggested for CO gas regulation of this channel and does not involve an interaction with either the "Ca bowl" or residues distal to this Ca(2+)-sensing domain. These data show that BK(Ca) is a K(+) channel target of H(2)S, and suggest a mechanism to explain the H(2)S-dependent component of O(2) sensing in the carotid body.
authors.affiliation: Division of Pathophysiology and Repair, School of Biosciences, Cardiff University, Cardiff, UK.
authors.forename: Vsevolod
authors.initials: V
authors.lastname: Telezhkin
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Brazier
authors.forename: Sebastien H
authors.initials: SH
authors.lastname: Cayzac
authors.forename: William J
authors.initials: WJ
authors.lastname: Wilkinson
authors.forename: Daniela
authors.initials: D
authors.lastname: Riccardi
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kemp
mesh_terms: D000393:Air Pollutants / Q000494:pharmacology*; D000818:Animals; D002344:Carotid Body / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D004594:Electrophysiology; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007150:Immunohistochemistry; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors* / Q000235:genetics; D008297:Male; D009154:Mutation; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D011190:Potassium Cyanide / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D000393:Air Pollutants; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D012333:RNA, Messenger; D011994:Recombinant Proteins; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D011190:Potassium Cyanide; D006862:Hydrogen Sulfide