title: Electrophysiological properties of the hypokalaemic periodic paralysis mutation (R528H) of the skeletal muscle alpha 1s subunit as expressed in mouse L cells.
abstract: Hypokalaemic periodic paralysis (HypoPP) is an autosomal dominant muscle disease which has been linked to point mutations in the skeletal muscle L-type calcium channel alpha 1 subunit (alpha 1s). Here, we have introduced one of the point mutations causing HypoPP (R528H) into cDNA of the rabbit alpha 1s. Expression of either the wild-type alpha 1s or the mutant R528H alpha 1s (alpha 1s-R528H) subunits was obtained in mouse Ltk- cells using a selectable expression vector. The alpha 1s-R528H subunit led to the expression of functional L-type Ca2+ channels. Corresponding whole-cell Ba2+ currents exhibit very slow activation and inactivation kinetics, typical for recombinant skeletal Ca2+ channel currents. Voltage-dependent activation and inactivation properties were similar for alpha 1s- and alpha 1s-R528H, as well as their sensitivity to the dihydropyridine agonist Bay K 8644. Differences in alpha 1s- and alpha 1s-R528H-directed channels reside in the Ba2+ current density, which was significantly reduced 3.2 fold in cells expressing alpha 1s-R528H. It was concluded that the R528H mutation af alpha 1s results in minor differences in the electrophysiological properties but significantly reduces the whole-cell Ca2+ channel current in its amplitude.
authors.affiliation: INSERM U134, Fédération de Neurologie, Hôpital de la Salpêtrière, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Lapie
authors.forename: C
authors.initials: C
authors.lastname: Goudet
authors.forename: J
authors.initials: J
authors.lastname: Nargeot
authors.forename: B
authors.initials: B
authors.lastname: Fontaine
authors.forename: P
authors.initials: P
authors.lastname: Lory
mesh_terms: D000818:Animals; D001464:Barium / Q000378:metabolism; D001483:Base Sequence; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D020746:Calcium Channels, L-Type; D004594:Electrophysiology; D017136:Ion Transport; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000503:physiopathology*; D010245:Paralyses, Familial Periodic / Q000235:genetics / Q000503:physiopathology*; D017354:Point Mutation; D011817:Rabbits; D014162:Transfection
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D001464:Barium