Modulation of human neuronal α1E-type calcium channel by α2δ-subunit

Abstract

Calcium channels are composed of a pore-forming subunit, α1, and at least two auxiliary subunits, β- and α2δ-subunits. It is well known that β-subunits regulate most of the properties of the channel. The function of α2δ-subunit is less understood. In this study, the effects of the calcium channel α2δ-subunit on the neuronal α1E voltage-gated calcium channel expressed in Xenopus oocytes was investigated without and with simultaneous coexpression of either the β1b- or the β2a-subunit. Most aspects of α1E function were affected by α2δ. Thus α2δ caused a shift in the current-voltage and conductance-voltage curves toward more positive potentials and accelerated activation, deactivation, and the installation of the inactivation process. In addition, the efficiency with which charge movement is coupled to pore opening assessed by determining ratios of limiting conductance to limiting charge movement was decreased by α2δ by factors that ranged from 1.6 ( P < 0.01) for α1E-channels to 3.0 ( P < 0.005) for α1Eβ1b-channels. These results indicate that α2δ facilitates the expression and the maturation of α1E-channels and converts these channels into molecules responding more rapidly to voltage.