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Research Paper

Comparative effects of H⁺ and Ca²⁺ on large-conductance Ca²⁺- and voltage-gated Slo1 K⁺ channels

Shangwei Hou, Frank T. Horrigan, Rong Xu, Stefan H. Heinemann and Toshinori Hoshi

Large-conductance Ca²⁺- and voltage-gated Slo1 BK channels are allosterically activated by depolarization and intracellular ligands such as Ca²⁺. Of the two high-affinity Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ is more effective in relative stabilization of the open conformation than H⁺. Calculations using the Debye-Hückel formulation 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 Ca²⁺, 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 ligand bound and transmits qualitatively different information to the channel's permeation gate.

Authors

Shangwei Hou

University of Pennsylvania; Philadelphia, PA USA

Frank T. Horrigan

Baylor College of Medicine; Houston, TX USA

Rong Xu

University of Pennsylvania; Philadelphia, PA USA

Stefan H. Heinemann

Friedrich Schiller University; Jena, Germany

Toshinori Hoshi Corresponding author: hoshi@hoshi.org

University of Pennsylvania