Cloning, chromosomal localization, and functional expression of the alpha 1 subunit of the L-type voltage-dependent calcium channel from normal human heart

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 13; pp. 6228 - 6232
• Main Authors: Schultz, D, Mikala, G, Yatani, A, Engle, D B, Iles, D E, Segers, B, Sinke, R J, Weghuis, D O, Klöckner, U, Wakamori, M
• Format: Journal Article
• Language: English
• Published: United States National Acad Sciences 01.07.1993
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Blotting, Northern; Calcium Channels; Chromosome Mapping; Chromosomes, Human, Pair 12; Cloning, Molecular; Cricetinae; DNA - chemistry; DNA - isolation & purification; Humans; In Situ Hybridization; Molecular Sequence Data; Myocardium - metabolism; Rabbits; Rats
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.13.6228

A unique structural variant of the cardiac L-type voltage-dependent calcium channel alpha 1 subunit cDNA was isolated from libraries derived from normal human heart mRNA. The deduced amino acid sequence shows significant homology to other calcium channel alpha 1 subunits. However, differences from the rabbit heart alpha 1 include a shortened N-terminus, a unique C-terminal insertion, and both forms of an alternatively spliced motif IV S3 region. The shortened N-terminus provides optimal access to consensus sequences thought to facilitate translation. Northern blot analysis revealed a single hybridizing mRNA species of 9.4 kb. The gene for the human heart alpha 1 subunit was localized specifically to the distal region of chromosome 12p13. The cloned alpha 1 subunit was expressed in Xenopus oocytes and single-channel analyses revealed native-like pharmacology and channel properties.