Mg2+ block unmasks Ca2+/Ba2+ selectivity of alpha 1G T-type calcium channels

We have examined permeation by Ca2+ and Ba2+, and block by Mg2+, using whol e-cell recordings from alpha 1G T-type calcium channels stably expressed in HEK 293 cells. Without Mg-0(2+), inward currents were comparable with Ca2 and Ba2+. Surprisingly, three other results indicate that alpha 1G is actu ally selective for Ca2+ over Ba2+. 1) Mg2+ block is similar to7-fold more p otent with Ba2+ than with Ca2+. With near-physiological (1 mM) Mg-0(2+), in ward currents were similar to3-fold larger with 2 mM Ca2+ than with 2 mM Ba 2+. The stronger competition between Ca2+ and Mg2+ implies that Ca2+ binds more tightly than Ba2+. 2) Outward currents (carried by Na+) are blocked mo re strongly by Ca2+ than by Ba2+. 3) The reversal potential is more positiv e with Ca2+ than with Ba2+, thus P-Ca > P-Ba. We conclude that alpha 1G can distinguish Ca2+ from Ba2+, despite the similar inward currents in the abs ence of Mg-0(2+). Our results can be explained by a 2-site, 3-barrier model if Ca2+ enters the pore 2-fold more easily than Ba2+ but exits the pore at a 2-fold lower rate.