Sequence and Expression of mRNAs Encoding the α ₁ and α ₂ Subunits of a DHP-Sensitive Calcium Channel

Abstract

Complementary DNAs were isolated and used to deduce the primary structures of the alpha 1 and alpha 2 subunits of the dihydropyridine-sensitive, voltage-dependent calcium channel from rabbit skeletal muscle. The alpha 1 subunit, which contains putative binding sites for calcium antagonists, is a hydrophobic protein with a sequence that is consistent with multiple transmembrane domains and shows structural and sequence homology with other voltage-dependent ion channels. In contrast, the alpha 2 subunit is a hydrophilic protein without homology to other known protein sequences. Nucleic acid hybridization studies suggest that the alpha 1 and alpha 2 subunit mRNAs are expressed differentially in a tissue-specific manner and that there is a family of genes encoding additional calcium channel subtypes.

Evidence for the existence of a cardiac specific isoform of the α1 subunit of the voltage dependent calcium channel

“…Electrophysiological and pharmacological data are consistent with the presence of tissue specific isoforms of the Ltype VDCC, in skeletal muscle, brain, heart, and vascular smooth muscle. The cyi subunit from skeletal muscle has been cloned and sequenced [12,13]. Using molecular cloning and Northern analysis, we present further evidence in favor of the existence of a heart specific isoform of the CYI subunit of the VDCC.…”

Tissue-specific expression of calcium channels

“…The purified complex contains four proteins (Figure 2) (Flockerzi et al 1986, Hymel et al 1988, Nunoki et al 1989, Mundiiia-Weilenmann et al 1991. The primary sequences of these proteins have been deduced by cloning their corresponding cDNAs from rabbit skeletal muscle (Tanabe et al 1987, Ellis et al 1988, Ruth et al 1989, Jay et al 1990. By using these cDNAs as probes, different a, and 8 subunits have been cloned from heart, smooth muscle, endocrine, and neuronal cells.…”

“…The skeletal muscle a,/6 subunit (&Al) is a glycosylated membrane protein of 125,018 D (Ellis et al 1988), which is apparently highly conserved in most tissues. In the skeletal muscle, the primary protein product of the a,/8 gene is processed posttranslationally by proteolysis resulting in an aI protein containing amino acids l-934 and a 8 protein containing amino acids 935-1080 (De Jongh et al 1990).…”

“…Immunoblots (Norman et al 1987) and Northern blots (Ellis et al 1988 show that similar or identical a@ subunits exist in skeletal muscle, heart, brain, vascular, and intestinal smooth muscle. Two identical C@ cDNAs have been isolated from rabbit skeletal muscle and human brain (Williams et al 1992a), whereas the a,/6 cDNA isolated from rat brain (Rim et al 1992) predicts an identical 8 protein and a splice variant of the processed az protein.…”

Polymerase chain reaction cloning of L‐type calcium channel sequences from the heart and the brain

“…Complementary DNA sequence for the cd subunit from rabbit skeletal muscle has been determined by Tanabe et al [5]. Ellis et al have determined the cDNA sequence for the al and ~2 subunits of the rabbit skeletal muscle calcium channel [9]. More recently, Mikami et al reported the primary amino acid sequence of an c~l subunit from the heart [10], and Koch et al reported partial amino acid sequence of al subunits from rat brain and aorta [11].…”