Several cDNAs encoding an isoform of the alpha-1 subunit of the voltage-dependent calcium channel were isolated from rat brain cDNA libraries. The complete nucleotide sequence of 6975 bp encodes a protein of 1634 amino acids, which corresponds to an M(r) of 186,968. The protein exhibits 71% and 76% homology to skeletal and cardiac alpha-1 subunits, respectively. When compared with skeletal and cardiac alpha-1 isoforms, the rat brain protein is intermediate in size at the amino terminus and shorter at the carboxyl terminus. Multiple subtypes of this alpha-1 isoform cDNA were characterized. These are indicative of alternative splicing of a primary transcript and encode three variants between motif I and motif II and two within the S3 region of motif IV. Thus, multiple isoforms of this rat brain alpha-1 subunit are possible.