Mg2+ Block Unmasks Ca2+/Ba2+ Selectivity of α1G T-Type Calcium Channels

AbstractWe have examined permeation by Ca2+ and Ba2+, and block by Mg2+, using whole-cell recordings from α1G T-type calcium channels stably expressed in HEK 293 cells. Without Mgo2+, inward currents were comparable with Ca2+ and Ba2+. Surprisingly, three other results indicate that α1G is actually selective for Ca2+ over Ba2+. 1) Mg2+ block is ∼7-fold more potent with Ba2+ than with Ca2+. With near-physiological (1mM) Mgo2+, inward currents were ∼3-fold larger with 2mM Ca2+ than with 2mM Ba2+. The stronger competition between Ca2+ and Mg2+ implies that Ca2+ binds more tightly than Ba2+. 2) Outward currents (carried by Na+) are blocked more strongly by Ca2+ than by Ba2+. 3) The reversal potential is more positive with Ca2+ than with Ba2+, thus PCa>PBa. We conclude that α1G can distinguish Ca2+ from Ba2+, despite the similar inward currents in the absence of Mgo2+. 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