Evidence for a specific site for modulation of calcium channel activation by external calcium ions

We have investigated the effect of permeant ion species on activation of transiently expressed neuronal alpha1A Ca channels. Equimolar replacement of Ba with Ca resulted in a consistent depolarizing shift of the half-activation potential whose magnitude (∼10 mV) was constant over a range of 2 to 100 mM permeant ion, suggesting that the effects of Ca ions were fully developed at concentrations below 2 mM and indicating that Ba and Ca screened surface charges equally. In mixtures of Ba and Ca at constant divalent cation concentration the voltage-shift, as a function of Ca mole fraction, was well described by a model in which Ba and Ca compete for a single site but only Ca ions produce a gating effect. Overall, our data are consistent with Ca ions exerting their effects on activation via a specific regulatory site.