The skeletal muscle-specific dihydropyridine-sensitive calcium channel is a critical component of excitation-contraction coupling in skeletal muscle. A recessive mutation in mice, muscular dysgenesis (mdg), has previously been described as resulting in defective excitation-contraction coupling. Although the channel-forming subunit (ai) of the skeletal calcium channel is not detectable immunologically, specific mRNA of normal size is present in dysgenic muscle. cDNA for this calcium channel α1 subunit has now been cloned from dysgenic muscle and sequenced in its entirety. A single nucleotide deletion occurs at nucleotide 4010 of the cDNA, resulting in a shift of the translational reading frame. The mutation has been confirmed by direct sequencing of PCR products from homozygous mutant and normal muscle. The mutant polypeptide is predicted to contain the first three repeating domains, five of the normal six transmembrane helices of the last repeating domain, and an altered and truncated C terminus. The mature mRNA encoding the dysgenic α1 subunit appears to be labile. It is possible that premature termination of translation renders the mutant mRNA subject to degradation by nucleases. This work resolves a long-standing controversy on the nature of the primary genetic defect in muscular dysgenesis.
|Original language||English (US)|
|Number of pages||4|
|Journal||Journal of Biological Chemistry|
|State||Published - 1992|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology