THE AMINO-TERMINUS OF A CALCIUM-CHANNEL BETA-SUBUNIT SETS RATES OF CHANNEL INACTIVATION INDEPENDENTLY OF THE SUBUNITS EFFECT ON ACTIVATION

There is molecular diversity in both alpha(1) and beta subunits of voltage-gated Ca2+ channels. Coupling between voltage sensing and pore opening of the C-type alpha(1) (alpha(1C)) is improved by the type 2 beta subunit (beta(2)), and E-type alpha(1) beta complexes inactivate at different rates depending on the nature of beta. We compared the effects of type 1 and 2 beta subunits on activation of the human E-type alpha(1) (alpha(1E)) with the effects they have on inactivation, as seen in Xenopus oocytes. The beta subtypes stimulated activation in similar fashion but affected inactivation differently, and even in opposing directions. beta subunits have a common central core but differ in their N- and C-termini and in a central region. N-terminal chimeras between beta(1) and beta(2) subunits that have opposing effects on inactivation resulted in the reciprocal transfer of their effects. We conclude that regulation of activation and inactivation of alpha(1) by beta are separable events and that the N-terminus of beta is one of the structural determinants important in setting the rate and voltage at which an al inactivates.