title: New molecular determinant for inactivation of the human L-type alpha1C Ca2+ channel.
abstract: Molecular cloning of the human fibroblast Ca2+ channel pore-forming alpha1C subunit revealed (Soldatov, 1992. Proc. Natl. Acad. Sci. USA 89:4628-4632) a naturally occurring mutation g2254 --> a that causes the replacement of the conservative alanine for threonine at the position 752 at the cytoplasmic end of transmembrane segment IIS6. Using stably transfected HEK293 cell lines, we have compared electrophysiological properties of the conventional alpha(1C,77) human recombinant L-type Ca2+ channel with those of its mutated isoform alpha(1C,94) containing the A752T replacement. Comparative quantification of steady-state availability of the current carried by alpha(1C,94) and alpha(1C,77) showed that A752T mutation prevented a large (approximately 25%) fraction of the current carried by Ca2+ or Ba2+ from fully inactivating. This mutation, however, did not appear to alter significantly the Ca2+-dependence and kinetics of decay of the inactivating fraction of the current or its voltage-dependence. The data suggests that Ala752 at the cytoplasmic end of IIS6 might serve as a molecular determinant of the Ca2+ channel inactivation, possibly regulating the voltage-dependence of its availability.
authors.affiliation: National Institute on Aging, NIH, Gerontology Research Center, Baltimore, MD 21224, USA.
authors.forename: N M
authors.initials: NM
authors.lastname: Soldatov
authors.forename: S
authors.initials: S
authors.lastname: Zhenochin
authors.forename: B
authors.initials: B
authors.lastname: AlBanna
authors.forename: D R
authors.initials: DR
authors.lastname: Abernethy
authors.forename: M
authors.initials: M
authors.lastname: Morad
mesh_terms: D000409:Alanine; D019943:Amino Acid Substitution; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000502:physiology*; D002460:Cell Line; D003001:Cloning, Molecular; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D007668:Kidney; D008564:Membrane Potentials / Q000502:physiology; D017354:Point Mutation; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D013912:Threonine; D014162:Transfection
chemical_list: D020746:Calcium Channels, L-Type; D011994:Recombinant Proteins; D013912:Threonine; D000409:Alanine