Molecular cloning of calcium channel alpha(2)delta-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 alpha(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.
Chu
Po-Ju
PJ
Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, IL 61801, Urbana, USA. pojuchu@uiuc.edu
Best
Philip M
PM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D020746:Calcium Channels, L-Type; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004553:Electric Conductivity; D005786:Gene Expression Regulation; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D032342:Muscle Cells / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics; D021122:Protein Subunits; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment
C486060:Cacna2d1 protein, rat; C478374:Cacna2d2 protein, rat; C478375:Cacna2d3 protein, rat; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D018076:DNA, Complementary; D020033:Protein Isoforms; D021122:Protein Subunits; D007334:Insulin-Like Growth Factor I