Primary structure of a calcium channel that is highly expressed in the rat cerebellum

Previous molecular cloning experiments showed that multiple isoforms of the alpha 1 subunit of voltage-gated Ca channels are expressed in the mammalian brain (designated rbA, rbB, rbC, and rbD). We report here the isolation and characterization of cDNAs encoding the rat brain class A (rbA) Ca channel. The rbA-126 cDNA encodes a 2212-amino acid protein that shares 33% sequence identity with the alpha 1 subunits of cardiac and skeletal muscle dihydropyridine-sensitive Ca channels. When compared with other Ca channels, the rbA channel is notably different in both the carboxyl terminus and in a large (474-amino acid) hydrophilic segment between domains II and III. Northern blot analysis shows that rbA transcripts are expressed in all regions of the rat central nervous system, but most prominently in the cerebellum. A more widespread distribution of rbA Ca channels is indicated by PCR analysis, which demonstrates the presence of class A transcripts in the rat heart and pituitary but not in the spleen, kidney, or liver. The rbA cDNA appears to encode a Ca channel alpha 1 subunit that is distinct from the dihydropyridine-sensitive Ca channel sequences and that is expressed in a variety of excitable cells.