APStracts 3:0165C, 1996.

Identification of a second region of the [beta] subunit involved in regulation of calcium channel inactivation . Qin, Ning, Riccardo Olcese, Jianming Zhou, Olga A. Cabello, Lutz Birnbaumer, and Enrico Stefani. Departments of Anesthesiology and Biological Chemistry and Molecular Biology Institute University of California Los Angeles, CA 90095, Department of Molecular Genetics, Baylor College of Medicine, Houston, TX 770303

APStracts 3:0165C, 1996.

Previous studies showed that N-termini of the type 1 and 2 [beta] subunits modulate the rate at which the neuronal [alpha]1E calcium channel inactivates in response to voltage and that they do so independently of their common effect to stimulate activation by voltage (1). By constructing N-terminal deletions of several splice variants of [beta] subunits, we have now found differences in the way they affect the rate of [alpha]1E inactivation that leed 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 between all known [beta] subunits, and exists in two lengths (long and short), 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 for the N-termini, the segment 3 does not affect the regulation of channel activation by the [beta] subunit. In addition, the effect of the N-terminal segment prevails over that of the internal segment. This raises the posibilities that phosphorylation, others type of posttranslational modification, or interaction with other auxiliary calcium channel subunit may be necessary to unmask the regulatory effect of the internal segment.

Received 6 March 1996; accepted in final form 8 May 1996.
APS Manuscript Number C127-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 May 96