Calcium channel current of vascular smooth muscle cells: Extracellular protons modulate gating and single channel conductance

Abstract

Modulation of L-type Ca2+ channel current by extracellular pH (pH(o)) was studied in vascular smooth muscle cells from bovine pial and porcine coronary arteries. Relative to pH 7.4, alkaline pH reversibly increased and acidic pH reduced I(Ca). The efficacy of pH(o) in modulating I(Ca) was reduced when the concentration of the charge carrier was elevated ([Ca2+](o) or [Ba2+](o) varied between 2 and 110 mM). Analysis of whole cell and single Ca2+ channel currents suggested that more acidic pH(o) values shift the voltage-dependent gating (~ 15 mV per pH-unit) and reduce the single Ca2+ channel conductance g(Ca) due to screening of negative surface charges. pH(o) effects on g(Ca) depended on the pipette [Ba2+] ([Ba2+](p)), pK*, the pH providing 50% of saturating conductance, increased with [Ba2+](p) according to pK*, = 2.7-2·log {[Ba2+](p)} suggesting that protons and Ba2+ ions compete for a binding site that modulates g(Ca). The above mechanisms are discussed in respect to their importance for Ca2+ influx and vasotonus.