Distribution, Splicing and Glucocorticoid-Induced Expression of Cardiacα1Candα1DVoltage-gated Ca2+Channel mRNAs

Abstract

Dihydropyridine-sensitive voltage-gated (l-type) Ca2+channels play an essential role in cardiac and smooth muscle excitation-contraction coupling. Transcripts for the two pore-forming subunits ofl-type Ca2+channels,α1Candα1Dhave been detected in heart and lung; however, distribution, structure and regulated expression of these channel subunit mRNAs have not been examined in detail. Here we use RNase protection and RT-PCR assays to identify cardiac-specific features of expression of the two channel mRNAs. First, expression ofα1DmRNA is found in lung, aorta and atrium, but is not detected in ventricle. Limited expression ofα1DmRNA is also seen in enriched preparations of cardiac myocytes: it is significant in atrial myocytes, but not in ventricular myocytes. Second, RT-PCR analyses indicate that atrialα1Dchannels exclusively contains the 15-amino acid insertion between third and fourth segments in repeat IV. Finally, expression ofα1CmRNA, but notα1DmRNA, is up-regulated by glucocorticoids in atrium and ventricle: adrenalectomy and subsequent injection of the glucocorticoid agonist dexamethasone decreased and increased the channel message, respectively. Dexamethasone also significantly increased the number of dihydropyridine-binding sites in ventricle. In contrast,α1CmRNA levels were glucocorticoid-insensitive in lung and aorta. Thus, basal and glucocorticoid-induced expression, and splicing of the twol-type Ca2+channelα1subunit transcripts are tissue specifically controlled in atria and ventricles of rat heart.