Effects of the external pH on Ca channels: experimental studies and theoretical considerations using a two-site, two-ion model

Abstract

Some effects of the external pH on Ca channels were studied in a hybridoma cell line (mAb-7B), by using the whole-cell configuration of the patch-clamp technique. As the pH was lowered, both the activation and the inactivation curves shifted toward less negative membrane potentials, suggesting a pH-induced decrease of an external negative surface potential, sensed by the mechanism of gating. The potential for half-activation, V1/2, and that for half-inactivation, Vh, were related by a straight line with a slope of one. The inward current varied exponentially with V1/2, as would be expected if the field inside the channel and the Ca2+ concentration at the entrance were sensitive to the surface potential. However, the reversal potential and the outward current were unaltered by changes in the pH. Under the hypothesis that the channel senses the surface potential, all these results, as well as the nernstian behavior of the reversal potential with respect to Ca2+, observed in previous studies, are accounted for by a three-barrier, two-ion model for a channel, provided it is assumed that the potential in the channel drops almost entirely across the barrier adjacent to the external solution.