Modulation of cloned neuronal calcium channels through membrane-delimited pathway.

Modulation of voltage-gated Ca2+ channels by the receptor coupled GTP-binding proteins (G-proteins) is essential for controlling secretion and muscle contraction. We have expressed cloned Ca2+ channels in dysgenic myotubes to study G-protein modulation through the membrane-delimited pathway. The results obtained by the expression of alpha 1B channels and mutant channels of alpha 1B suggest that the two effects observed in G-protein modulated N-type channels (depression of current and slowing of activation) are through two independent mechanisms. In addition, neither the region linking repeat II and III nor carboxy-terminal region, which were demonstrated in L-type channels to determine some of their specific functions, are directly involved in G-protein modulation. The results obtained by the expression of the alpha 1A channel suggest that this channel is modulated through a novel membrane-delimited pathway that may not involve G-protein activation.