title: Comparative effects of H+ and Ca2+ on large-conductance Ca2+- and voltage-gated Slo1 K+ channels.
abstract: Large-conductance Ca(2+)- and voltage-gated Slo1 BK channels are allosterically activated by depolarization and intracellular ligands such as Ca(2+). Of the two high-affinity Ca(2+) sensors present in the channel, the RCK1 sensor also mediates H(+)-dependent activation of the channel. In this study, we examined the comparative mechanisms of the channel activation by Ca(2+) and H(+). Steady-state macroscopic conductance-voltage measurements as well as single-channel openings at negative voltages where voltage-sensor activation is negligible showed that at respective saturating concentrations Ca(2+) is more effective in relative stabilization of the open conformation than H(+). Calculations using the Debye-Hückel formalism suggest that small structural changes in the RCK1 sensor, on the order of few angstroms, may accompany the H(+)-mediated opening of the channel. While the efficacy of H(+) in activation of the channel is less than that of Ca(2+), H(+) more effectively accelerates the activation kinetics when examined at the concentrations equipotent on macroscopic voltage-dependent activation. The RCK1 sensor therefore is capable of transducing the nature of the bound ligand and transmits qualitatively different information to the channel's permeation gate.
authors.affiliation: Department of Physiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Shangwei
authors.initials: S
authors.lastname: Hou
authors.forename: Frank T
authors.initials: FT
authors.lastname: Horrigan
authors.forename: Rong
authors.initials: R
authors.lastname: Xu
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Heinemann
authors.forename: Toshinori
authors.initials: T
authors.lastname: Hoshi
mesh_terms: D002118:Calcium / Q000494:pharmacology*; D002460:Cell Line; D004594:Electrophysiology; D006801:Humans; D007700:Kinetics; D051662:Kv1.1 Potassium Channel / Q000502:physiology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000187:drug effects*; D008024:Ligands; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects*; D011487:Protein Conformation; D011522:Protons
chemical_list: C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D008024:Ligands; D024642:Potassium Channels, Voltage-Gated; D011522:Protons; D051662:Kv1.1 Potassium Channel; D002118:Calcium