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

Abstract

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.