title: Haem can bind to and inhibit mammalian calcium-dependent Slo1 BK channels.
abstract: Haem is essential for living organisms, functioning as a crucial element in the redox-sensitive reaction centre in haemproteins. During the biogenesis of these proteins, the haem cofactor is typically incorporated enzymatically into the haem pockets of the apo-haemprotein as the functionally indispensable prosthetic group. A class of ion channel, the large-conductance calcium-dependent Slo1 BK channels, possesses a conserved haem-binding sequence motif. Here we present electrophysiological and structural evidence showing that haem directly regulates cloned human Slo1 channels and wild-type BK channels in rat brain. Both oxidized and reduced haem binds to the hSlo1 channel protein and profoundly inhibits transmembrane K+ currents by decreasing the frequency of channel opening. This direct regulation of the BK channel identifies a previously unknown role of haem as an acute signalling molecule.
authors.affiliation: Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Xiang Dong
authors.initials: XD
authors.lastname: Tang
authors.forename: Rong
authors.initials: R
authors.lastname: Xu
authors.forename: Mark F
authors.initials: MF
authors.lastname: Reynolds
authors.forename: Maria L
authors.initials: ML
authors.lastname: Garcia
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Heinemann
authors.forename: Toshinori
authors.initials: T
authors.lastname: Hoshi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D006418:Heme / Q000378:metabolism* / Q000494:pharmacology*; D006427:Hemin / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008969:Molecular Sequence Data; D009154:Mutation; D010084:Oxidation-Reduction; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats
chemical_list: C494841:KCNMA1 protein, human; C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D006418:Heme; D006427:Hemin