MODULATION OF HUMAN NEURONAL ALPHA(1E)-TYPE CALCIUM-CHANNEL BY ALPHA(2)DELTA-SUBUNIT

Calcium channels are composed of a pore-forming subunit, alpha(1), and at least two auxiliary subunits, beta- and alpha(2) delta-subunits. I t is well known that beta-subunits regulate most of the properties of the channel. The function of alpha(2) delta-subunit is less understood . In this study, the effects of the calcium channel alpha(2) delta-sub unit on the neuronal alpha(1E) voltage-gated calcium channel expressed in Xenopus oocytes was investigated without and with simultaneous coe xpression of either the beta(1b)- or the beta(2A)-subunit. Most aspect s of alpha(1E) function were affected by alpha(2) delta. Thus alpha(2) delta caused a shift in the current-voltage and conductance-voltage c urves toward more positive potentials and accelerated activation, deac tivation, and the installation of the inactivation process. In additio n, the efficiency with which charge movement is coupled to pore openin g assessed by determining ratios of limiting conductance to limiting c harge movement was decreased by alpha(2) delta by factors that ranged from 1.6 (P < 0.01) for alpha(1E)-channels to 3.0 (P < 0.005) for alph a(1E)beta(1b)-channels. These results indicate that alpha(2) delta fac ilitates the expression and the maturation of alpha(1E)- channels and converts these channels into molecules responding more rapidly to volt age.