title: Functional regulation of BK potassium channels by γ1 auxiliary subunits.
abstract: Many K(+) channels are oligomeric complexes with intrinsic structural symmetry arising from the homo-tetrameric core of their pore-forming subunits. Allosteric regulation of tetramerically symmetric proteins, whether by intrinsic sensing domains or associated auxiliary subunits, often mirrors the fourfold structural symmetry. Here, through patch-clamp recordings of channel population ensembles and also single channels, we examine regulation of the Ca(2+)- and voltage-activated large conductance Ca(2+)-activated K(+) (BK) channel by associated γ1-subunits. Through expression of differing ratios of γ1:α-subunits, the results reveal an all-or-none functional regulation of BK channels by γ-subunits: channels either exhibit a full gating shift or no shift at all. Furthermore, the γ1-induced shift exhibits a state-dependent labile behavior that recapitulates the fully shifted or unshifted behavior. The γ1-induced shift contrasts markedly to the incremental shifts in BK gating produced by 1-4 β-subunits and adds a new layer of complexity to the mechanisms by which BK channel functional diversity is generated.
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Vivian
authors.initials: V
authors.lastname: Gonzalez-Perez
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Xia
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lingle
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D006801:Humans; D015640:Ion Channel Gating; D051379:Mice; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism*; D013997:Time Factors; D014982:Xenopus laevis
chemical_list: C539913:LRRC26 protein, human; D009363:Neoplasm Proteins; D021122:Protein Subunits
keywords: Slo1 channels; allostery; asymmetry