Mutually exclusive exon splicing of the cardiac calcium channel alpha 1 subunit gene generates developmentally regulated isoforms in the rat heart.
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.
Diebold
R J
RJ
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, OH 45267-0575.
Koch
W J
WJ
Ellinor
P T
PT
Wang
J J
JJ
Muthuchamy
M
M
Wieczorek
D F
DF
Schwartz
A
A
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
D015220:Calcium Channels; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger