CLONING, CHROMOSOMAL LOCALIZATION, AND FUNCTIONAL EXPRESSION OF THE ALPHA-1-SUBUNIT OF THE L-TYPE VOLTAGE-DEPENDENT CALCIUM-CHANNEL FROM NORMAL HUMAN HEART

A unique structural variant of the cardiac L-type voltage-dependent ca lcium channel alpha1, subunit cDNA was isolated from libraries derived from normal human heart mRNA. The deduced amino acid sequence shows s ignificant homology to other calcium channel alpha1 subunits. However, differences from the rabbit heart alpha1 include a shortened N-termin us, 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. North ern blot analysis revealed a single hybridizing mRNA species of 9.4 kb . The gene for the human heart alpha1 subunit was localized specifical ly to the distal region of chromosome 12p13. The cloned alpha1 subunit was expressed in Xenopus oocytes and single-channel analyses revealed native-like pharmacology and channel properties.