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 calcium channel alpha1, subunit cDNA was isolated from libraries derived from normal human heart mRNA. The deduced amino acid sequence shows significant homology to other calcium channel alpha1 subunits. However, differences from the rabbit heart alpha1 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 alpha1 subunit was localized specifically 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.