Dependence of ion flow through channels on the density of fixed charges at the channel opening. Voltage control of inverse titration curves.

Model calculations were done to investigate the effect of titratable fixed charges at channel openings on ion flow through open channels. The current titration curves (channel current vs. bulk pH) can assume the shape expected from the change of the ionic surface concentration with pH (c-control), or be inverted, i.e., follow the change of the electrical field within the membrane (V-control). The relationships were explored pars pro toto for Goldman-Hodgkin-Katz channels, two-barrier one-site channels and six-barrier five-site channels. With net current flowing in the direction of the concentration gradient and from the titrated fixed charge layer into the channel, c-control is the sign of low channel occupancy (entrance-step limitation) and V-control the sign of high channel occupancy (exit-step limitation). At intermediate occupancy, the current titration curve can be nearly invariant to pH.