Increase in Ca2+ channel expression by deletions at the amino terminus of the cardiac alpha 1C subunit

Abstract

The alpha 1 subunit of the cardiac L-type Ca2+ channel (alpha 1C) is one of the many alternatively spliced products of a single gene that is expressed in a number of excitable tissues. Sequence comparison indicates that the amino terminus is a site of significant structural diversity. To explore the role of the amino terminus of alpha 1C in expression and function of Ca2+ channels, we constructed a series of deletion mutants of the rabbit cardiac alpha 1C subunit and expressed them in Xenopus oocytes. Deletions of up to 120 amino acids from the amino terminus increased both ionic and gating currents by 5- to 8-fold. Ca2+ currents induced by these mutants had voltage-dependent activation, inactivation, modulation by beta subunits, and single channel conductance similar to the wild type cardiac alpha 1C (wt alpha 1C). Thus, deletion of a major portion of the amino terminus of alpha 1C did not alter the three dimensional conformation essential for channel function, but enhanced the expression of Ca2+ channels in Xenopus oocytes. A deletion mutant lacking the first 171 amino acids did not yield any measurable current.