Distribution, splicing and glucocorticoid-induced expression of cardiac alpha 1C and alpha 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, alpha 1C and alpha 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 alpha 1D mRNA is found in lung, aorta and atrium, but is not detected in ventricle. Limited expression of alpha 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 exclusively contains the 15-amino acid insertion between third and fourth segments in repeat IV. Finally, expression of alpha 1C mRNA, but not alpha 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, alpha 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 alpha 1 subunit transcripts are tissue specifically controlled in atria and ventricles of rat heart.
Takimoto
K
K
Department of Pharmacology, University of Pittsburgh, PA, 15261, USA.
Li
D
D
Nerbonne
J M
JM
Levitan
E S
ES
D000595:Amino Acid Sequence; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology*; D004095:Dihydropyridines / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D008969:Molecular Sequence Data; D012326:RNA Splicing; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D005938:Glucocorticoids; D012333:RNA, Messenger; C038806:1,4-dihydropyridine; D003907:Dexamethasone