Molecular cloning of calcium channel α2δ-subunits from rat atria and the differential regulation of their expression by IGF-1

Calcium channels are multimeric proteins consisting of pore-forming (alpha(1)) and auxiliary (alpha(2)delta, beta, gamma) subunits. The auxiliary alpha(2)delta-subunit regulates calcium current density and activation/inactivation kinetics when co-expressed with some, but not all, alpha(1)-subunits. Here we report the differential expression of three alpha(2)delta-subunit cDNAs in rat atria, atrial myocytes and ventricle, and demonstrate that IGF-1 selectively increases the expression of the alpha(2)delta-3 mRNA in the atria. mRNA encoding the alpha(2)delta-1- and alpha(2)delta-2-subunits, but not the alpha(2)delta-3-subunit, is detected in the rat ventricle whereas all three transcripts are found in atrial tissue. Analysis of the rat alpha(2)delta-1 cDNA sequence indicates that the atria express the alpha(2)delta-1e alternatively spliced isoform of this gene. The complete cDNA sequences of the alpha(2)delta-2- and a(2)delta-3-subunits from rat atria were determined and found to share 96% and 95% identity, respectively, with their counterparts in mouse. Treatment of acutely cultured atrial myocytes with IGF-1 caused a significant increase of the amount of alpha(2)delta-3, but not alpha(2)delta-1 or alpha(2)delta-2, mRNA. Both L-type and T-type calcium currents are recorded from cardiac tissue although their expression is regionally specific and changes with age and physiological state. Differential regulation of the expression of alpha(2)delta-subunit genes is likely to contribute to alterations in the expression of calcium current in the mammalian heart. (C) 2003 Elsevier Science Ltd. All rights reserved.