Distribution, splicing and glucocorticoid induced expression of cardiac a(1C) and a(1D) voltage gated Ca²⁺ channel mRNAs

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 of L type Ca²⁺ channels, α(1C) and α(₁D) have 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 of α(1D) mRNA is found in lung, aorta and atrium, but is not detected in ventricle. Limited expression of α(1D) mRNA 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 atrial α(1D) channels exclusively contains the 15-amino acid insertion between third and fourth segments in repeat IV. Finally, expression of α(1C) mRNA, but not α(1D) mRNA, 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, α(1C) mRNA levels were glucocorticoid-insensitive in lung and aorta. Thus, basal and glucocorticoid-induced expression, and splicing of the two L-type Ca²⁺ channel α₁ subunit transcripts are tissue specifically controlled in atria and ventricles of rat heart.