title: Mutually exclusive exon splicing of the cardiac calcium channel alpha 1 subunit gene generates developmentally regulated isoforms in the rat heart.
abstract: Several clones were isolated from a rat genomic library in order to further characterize a region of variability within the third membrane-spanning region of the fourth motif (IVS3) of the L-type voltage-dependent calcium channel. We report here that this diversity arises from alternative splicing of a primary transcript containing a single pair of adjacent exons each encoding a unique sequence for the IVS3 region. Definitive proof of a mutually exclusive splicing mechanism was obtained by genomic mapping of flanking upstream and downstream exons and by extensive sequence analysis of the relevant exon/intron boundaries. S1 nuclease protection experiments revealed that both variant forms of the IVS3 were equally expressed in newborn and fetal rat heart, whereas only a single isoform predominated in adult rat heart. The results demonstrate the existence of an important developmentally regulated switch mediated by alternatively spliced exons in cardiac tissue at a time when major changes in excitation occur.
authors.affiliation: Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, OH 45267-0575.
authors.forename: R J
authors.initials: RJ
authors.lastname: Diebold
authors.forename: W J
authors.initials: WJ
authors.lastname: Koch
authors.forename: P T
authors.initials: PT
authors.lastname: Ellinor
authors.forename: J J
authors.initials: JJ
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Muthuchamy
authors.forename: D F
authors.initials: DF
authors.lastname: Wieczorek
authors.forename: A
authors.initials: A
authors.lastname: Schwartz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015220:Calcium Channels / Q000235:genetics*; D003001:Cloning, Molecular; D005091:Exons; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D015183:Restriction Mapping
chemical_list: D015220:Calcium Channels; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger