Key result
Cloned human cardiac L-type calcium channel alpha 1 subunit yields native-like ~24 pS conductance.
The successful cloning and functional expression of the human cardiac L-type calcium channel alpha-1 subunit provides a foundational tool for studying human-specific cardiac electrophysiology and pharmacology.
May facilitate targeted cardiac channel research; leaves open clinical translation pending human validation.
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.
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Schultz et al. (1993) studied Normal human heart. Cloned human cardiac L-type voltage-dependent calcium channel alpha 1 subunit cDNA was evaluated on Electrophysiological properties and single-channel conductance in Xenopus oocytes. The cloned human cardiac L-type voltage-dependent calcium channel alpha 1 subunit mapped to chromosome 12p13 and yielded native-like pharmacology with a mean slope conductance of 24 pS when expressed in Xenopus oocytes.
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