Inhibition of K(Ca)2.2 and K(Ca)2.3 channel currents by protonation of outer pore histidine residues.

ABSTRACT: Ion channels are often modulated by changes in extracellular pH, with most examples resulting from shifts in the ionization state of histidine residue(s) in the channel pore. The application of acidic extracellular solution inhibited expressed K(Ca)2.2 (SK2) and K(Ca)2.3 (SK3) channel currents, with K(Ca)2.3 (pIC(50) of approximately 6.8) being approximately fourfold more sensitive than K(Ca)2.2 (pIC(50) of approximately 6.2). Inhibition was found to be voltage dependent, resulting from a shift in the affinity for the rectifying intracellular divalent cation(s) at the inner mouth of the selectivity filter. The inhibition by extracellular protons resulted from a reduction in the single-channel conductance, without significant changes in open-state kinetics or open probability. K(Ca)2.2 and

SUBMITTER: Goodchild SJ 

PROVIDER: S-EPMC2757770 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature