STRUCTURES AND FUNCTIONS OF CALCIUM-CHANNEL BETA-SUBUNITS

Calcium channel beta subunits have profound effects on how alpha(1) su bunits perform. In this article we summarize our present knowledge of the primary structures of beta subunits as deduced from cDNAs and illu strate their different properties. Upon co-expression with alpha(1) su bunits, the effects of beta subunits vary somewhat between L-type and non-L-type channels mostly because the two types of channels have diff erent responses to voltage which are affected by beta subunits, such a s lone-lasting prepulse facilitation of alpha(1C) (absent in alpha(1E) ) and inhibition by G protein beta gamma dimer of alpha(1E), absent in alpha(1C). One beta subunit, a brain beta 2a splice variant that is p almitoylated, has several effects not seen with any of the others, and these are due to palmitoylation. We also illustrate the finding that functional expression of alpha(1) in oocytes requires a beta subunit e ven if the final channel shows no evidence for its presence. We propos e two structural models for Ca2+ channels to account for ''alpha(1) al one'' channels seen in cells with limited beta subunit expression. In one model, beta dissociates from the mature alpha(1) after proper fold ing and membrane insertion. Regulated channels seen upon co-expression of high levels of beta would then have subunit composition alpha(1)be ta In the other model, the ''chaperoning'' beta remains associated wit h the mature channel and ''alpha(1) alone'' channels would in fact be alpha(1)beta channels. Upon co-expression of high levels of beta the r egulated channels would have composition [alpha(1)beta]beta.