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 (α1) and auxiliary (α2δ, β, γ) subunits. The auxiliary α2δ-subunit regulates calcium current density and activation/inactivation kinetics when co-expressed with some, but not all, α1-subunits. Here we report the differential expression of three α2δ-subunit cDNAs in rat atria, atrial myocytes and ventricle, and demonstrate that IGF-1 selectively increases the expression of the α2δ-3 mRNA in the atria. mRNA encoding the α2δ-1- and α2δ-2-subunits, but not the α2δ-3-subunit, is detected in the rat ventricle whereas all three transcripts are found in atrial tissue. Analysis of the rat α2δ-1 cDNA sequence indicates that the atria express the α2δ-1e alternatively spliced isoform of this gene. The complete cDNA sequences of the α2δ-2- and α2δ-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 α2δ-3, but not α2δ-1 or α2δ-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 α2δ-subunit genes is likely to contribute to alterations in the expression of calcium current in the mammalian heart.