Primary Structure of the γ Subunit of the DHP-Sensitive Calcium Channel from Skeletal Muscle

Abstract

Affinity-purified, polyclonal antibodies to the gamma subunit of the dihydropyridine (DHP)-sensitive, voltage-dependent calcium channel have been used to isolate complementary DNAs to the rabbit skeletal muscle protein from an expression library. The deduced primary structure indicates that the gamma subunit is a 25,058-dalton protein that contains four transmembrane domains and two N-linked glycosylation sites, consistent with biochemical analyses showing that the gamma subunit is a glycosylated hydrophobic protein. Nucleic acid hybridization studies indicate that there is a 1200-nucleotide transcript in skeletal muscle but not in brain or heart. The gamma subunit may play a role in assembly, modulation, or the structure of the skeletal muscle calcium channel.

Identification of Three Novel Ca2+ Channel γ Subunit Genes Reveals Molecular Diversification by Tandem and Chromosome Duplication

“…We found expressed sequences corresponding to CACNG5 by PCR amplification of a human fetal kidney cDNA library but did not exclude the possibility of CACNG5 expression in the brain or other tissues. It is worth noting that several tissues that express multiple ␣ 1 , ␤, and ␣ 2 ␦ subunit isoforms, including testes, ovary, lung, pancreas, spleen, liver, and kidney, do not express ␥ 1 or ␥ 2 (Biel et al 1990;Jay et al 1990;Castellano and Perez-Reyes 1994;Yu 1995;Williams et al 1999). The ␥ 3 , ␥ 4 , and ␥ 5 isoforms are possible components of Ca 2+ channels in these tissues.…”

“…Expression of a single isoform in neurons distinguishes the ␥ subunit from other Ca 2+ channel subunits, which utilize genetic heterogeneity as an important mechanism for generating functional diversity in these cells. In addition, the expression of significant levels of either CACNG1 or CACNG2 mRNA has not been reported in tissues such as heart, kidney, and testis, which express high levels of other Ca 2+ channel subunits and produce measurable Ca 2+ currents (Jay et al 1990; Letts et al 1998). We therefore hypothesized the existence of additional ␥ subunit genes.…”

Mutations in voltage-gated L-type calcium channel: implications in cardiac arrhythmia

“…The first γ 1 subunit was cloned from skeletal muscle [44,45], whereas it was not expressed in cardiac muscle [46]. The γ subunit distinguishingly modulates the functions by altering both activation and inactivation properties of LTCC [46].…”

Voltage-Gated Calcium Channels

“…2) (Ruth et al 1989), whereas the g subunit is a glycoprotein with four transmembrane segments ( Fig. 2) (Jay et al 1990). The cloned a2 subunit has many glycosylation sites and several hydrophobic sequences (Ellis et al 1988), but biosynthesis studies indicate that it is an extracellular, extrinsic membrane glycoprotein, attached to the membrane through disulfide linkage to the d subunit ( Fig.…”