Electrophysiological properties of the hypokalaemic periodic paralysis mutation (R528H) of the skeletal muscle α 1S subunit as expressed in mouse L cells

FEBS Letters

Goudet, Cyril²  Nargeot, Joël²  Fontaine, Bertrand¹  Lory, Philippe²  Lapie, Pascale¹ 

[1] INSERM U134, Fédération de Neurologie, Hôpital de la Salp̌etrière, 75013 Paris, France;CRBM, CNRS UPR 9008 and INSERM U249, BP 5051, 1919 route de Mende, 34033 Montpellier cedex, France

关键词: Hypokalaemic periodic paralysis;    L-type Ca2+ channel;    Mouse L cell;    Skeletal α 1 subunit;    Transfection;   

DOI  :  10.1016/0014-5793(96)00173-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 α ₁ subunit (α _1S ). Here, we have introduced one of the point mutations causing HypoPP (R528H) into cDNA of the rabbit α _1S . Expression of either the wild-type α _1S or the mutant R528H α _1S (α ₁ S−R528H) subunit was obtained in mouse Ltk⁻ cell using a selectable expression vector. The α _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 α _1S -and α _{1S − R528H} , as well as their sensitivity to the dihydropyridine agonist Bay K 8644. Differences in α _1S -and α _1S−R528H -directed channels reside in the Ba²⁺ current density, which was significantly reduced 3.2 fold in cells expressing α _{1S − R528H} . It was concluded that the R528H mutation of α _1S results in minor differences in the electrophysiological properties but significantly reduces the whole-cell Ca²⁺ channel current in its amplitude.

【 授权许可】

Unknown