IDENTIFICATION OF A 2ND-REGION OF THE BETA-SUBUNIT INVOLVED IN REGULATION OF CALCIUM-CHANNEL INACTIVATION

Previous studies have shown that NH2 termini of the type 1 and 2 beta- subunits modulate the rate at which the neuronal alpha(1E) calcium cha nnel inactivates in response to voltage and that they do so independen tly of their common effect to stimulate activation by voltage (R. Olce se, N. Qin, T. Schneider, A. Neely, X. Wei, E. Stefani, and L. Birnbau mer, Neuron, 13: 1433-1438, 1994). By constructing NH2-terminal deleti ons of several splice variants of beta-subunits, we have now found dif ferences in the way they affect the rate of alpha(1E) inactivation tha t lead us to identify a second domain that also regulates the rate of voltage-induced inactivation of the Ca2+ channel. This second domain, named segment 3, lies between two regions of high-sequence identity be tween all known beta-subunits and exists in two lengths (long and shor t), each encoded in a separate exon. beta-Subunits with the longer 45- to 53-amino acid version cause the channel to inactivate more slowly than subunits with the shorter 7-amino acid version. As is the case fo r the NH2 terminus, the segment 3 does not affect the regulation of ch annel activation by the beta-subunit. In addition, the effect of the N H2-terminal segment prevails over that of the internal segment. This r aises the possibility that phosphorylation, other types of posttransla tional modification, or interaction with other auxiliary calcium chann el subunits may be necessary to unmask the regulatory effect of the in ternal segment.