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 alpha(1A) Ca channels. Equimolar rep lacement of Ba with Ca resulted in a consistent depolarizing shift of the half-activation potential whose magnitude (similar to 10 mV) was c onstant 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 a nd indicating that Ba and Ca screened surface charges equally. In mixt ures of Ba and Ca at constant divalent cation concentration the voltag e-shift, as a function of Ca mole fraction, was well described by a mo del in which Ba and Ca compete for a single site but only Ca ions prod uce a gating effect. Overall, our data are consistent with Ca ions exe rting their effects on activation via a specific regulatory site.