RT Journal Article SR Electronic T1 Molecular Cloning and Characterization of the Human Voltage-Gated Calcium Channel α2δ-4 Subunit JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 485 OP 496 DO 10.1124/mol.62.3.485 VO 62 IS 3 A1 Ning Qin A1 Susan Yagel A1 Mary-Lou Momplaisir A1 Ellen E. Codd A1 Michael R. D'Andrea YR 2002 UL http://molpharm.aspetjournals.org/content/62/3/485.abstract AB The voltage-gated calcium channel is composed of a pore-forming α1 subunit and several regulatory subunits: α2δ, β, and γ. We report here the identification of a novel α2δ subunit, α2δ-4, from the expressed sequence tag database followed by its cloning and characterization. The novel α2δ-4 subunit gene contains 39 exons spanning about 130 kilobases and is co-localized with theCHCNA1C gene (α1C subunit) on human chromosome 12p13.3. Alternative splicing of the α2δ-4 gene gives rise to four potential variants, a through d. The open reading frame of human α2δ-4a is composed of 3363 base pairs encoding a protein with 1120 residues and a calculated molecular mass of 126 kDa. The α2δ-4a subunit shares 30, 32, and 61% identity with the human calcium channel α2δ-1, α2δ-2, and α2δ-3 subunits, respectively. Primary sequence comparison suggests that α2δ-4 lacks the gabapentin binding motifs characterized for α2δ-1 and α2δ-2; this was confirmed by a [3H]gabapentin-binding assay. In human embryonic kidney 293 cells, the α2δ-4 subunit associated with CaV1.2 and β3 subunits and significantly increased CaV1.2/β3-mediated Ca2+influx. Immunohistochemical study revealed that the α2δ-4 subunit has limited distribution in special cell types of the pituitary, adrenal gland, colon, and fetal liver. Whether the α2δ-4 subunit plays a distinct physiological role in select endocrine tissues remains to be demonstrated.