The C terminus of the Ca channel alpha(1B) subunit mediates selective inhibition by G-protein-coupled receptors

Inhibition of calcium channels by G-protein-coupled receptors depends on th e nature of the G alpha subunit, although the G beta gamma complex is thoug ht to be responsible for channel inhibition. Ca currents in hypothalamic ne urons and N-type calcium channels expressed in HEK-293 cells showed robust inhibition by G(i)/G(o)-coupled galanin receptors (GalR1), but not by Gq-co upled galanin receptors (GalR2). However, deletions in the C terminus Of al pha (1B-1) produced Ca channels that were inhibited after activation of bot h GalR1 and GalR2. Inhibition of protein kinase C (PKC) also revealed Ca cu rrent modulation by GalR2. Imaging studies using green fluorescent protein fusions of the C terminus of alpha (1B) demonstrated that activation of the GalR2 receptor caused translocation of the C terminus of alpha (1B-1) to t he membrane and co-localization with G alphaq and PKC. Similar translocatio n was not seen with a C-terminal truncated splice variant, alpha (1B-2). Im munoprecipitation experiments demonstrated that G alphaq interacts directly with the C terminus of the alpha (1B) subunit. These results are consisten t with a model in which local activation of PKC by channel-associated G alp haq blocks modulation of the channel by G beta gamma released by Gq-coupled receptors.