DISTRIBUTION, SPLICING AND GLUCOCORTICOID-INDUCED EXPRESSION OF CARDIAC ALPHA(1C) AND ALPHA(1D) VOLTAGE-GATED CA2-RNAS( CHANNEL MESSENGER)

K. Takimoto, D. Li, J.M. Nerbonne and E.S. Levitan. Distribution, Spli cing and Glucocorticoid-induced Expression of Cardiac alpha(1C) and al pha(1D) Voltage-goted Ca2+ channel mRNAs. Journal of Molecular and Cel lular Cardiology (1997) 29, 3035-3042. Dihydropyridine-sensitive volta ge-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, alpha(1C) and alpha(1D ) have been detected in heart and lung; however, distribution, structu re and regulated expression of these channel subunit mRNAs have not be en 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 alpha(1D) mRNA is found in lung, aorta an d atrium, but is not detected in ventricle. Limited expression of alph a(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 alpha(1D) channels exclu sively contains the 15-amino acid insertion between third and fourth s egments in repeat IV. Finally, expression of alpha(1C) mRNA, but not a lpha(1D) mRNA, is up-regulated by glucocorticoids in atrium and ventri cle: adrenalectomy and subsequent injection of the glucocorticoid agon ist dexamethasone decreased and increased the channel message, respect ively. Dexamethasone also significantly increased the number of dihydr opyridine-binding sites in ventricle. In contrast, alpha(1C) mRNA leve ls were glucocorticoid-insensitive in lung and aorta. Thus, basal and glucocorticoid-induced expression, and splicing of the two L-type Ca2 channel alpha(1) subunit transcripts are tissue specifically controll ed in atria and ventricles of rat heart. (C) 1997 Academic Press Limit ed.