Résumé
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
1
S
). Here, we have introduced one of the point mutations causing HypoPP (R528H) into cDNA of the rabbit
α
1
S
. Expression of either the wild-type
α
1S or the mutant R528H
α
1
S
(
α
1
S−
R528
H) subunit was obtained in mouse Ltk
− cell using a selectable expression vector. The
α
1
S−
R528
H
subunit led to the expression of functional L-type Ca
2+ channels. Corresponding whole-cell Ba
2+ currents exhibit very slow activation and inactivation kinetics, typical for recombinant skeletal Ca
2+ channel currents. Voltage-dependent activation and inactivation properties were similar for
α
1
S
-and
α
1
S −
R528
H
, as well as their sensitivity to the dihydropyridine agonist Bay K 8644. Differences in
α
1
S
-and
α
1
S−
R528
H
-directed channels reside in the Ba
2+ current density, which was significantly reduced 3.2 fold in cells expressing
α
1
S −
R528
H
. It was concluded that the R528H mutation of
α
1
S
results in minor differences in the electrophysiological properties but significantly reduces the whole-cell Ca
2+ channel current in its amplitude.