Electrophysiological properties of the hypokalaemic periodic paralysis mutation (R528H) of the skeletal muscle alpha(1S) subunit as expressed in mouse L cells.
Electrophysiological properties of the hypokalaemic periodic paralysis mutation (R528H) of the skeletal muscle alpha(1S) subunit as expressed in mouse L cells.
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DOI：
10.1016/0014-5793(96)00173-1
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发表时间：
1996-03-18
期刊：
影响因子：
3.5
通讯作者：
Lory, P
中科院分区：
文献类型：
--
作者：
Lapie, P;Goudet, C;Lory, P
低钾性周期性麻痹（HypoPP）是一种常染色体显性肌肉疾病，其与骨骼肌L型钙通道α 1亚单位（α（1 S））的点突变有关。在此，我们将引起HypoPP的点突变之一（R528 H）引入兔α（1 S）的cDNA中。使用可选择的表达载体在小鼠Ltk（-）细胞中获得野生型α（1 S）或突变体R528 H α（1 S）（α（1 S-R528 H））亚基的表达。α（1 S-R528 H）亚基导致功能性L型Ca 2+通道的表达。相应的全细胞Ba 2+电流表现出非常缓慢的激活和失活动力学，典型的重组骨骼钙通道电流。电压依赖性激活和失活特性是相似的α（1 S）-和α（1 S-R528 H），以及他们的敏感性，二氢吡啶激动剂湾K 8644。α（1 S）-和α（1 S-R528 H）-定向通道的差异在于Ba 2+电流密度，其在表达α（1 S-R528 H）的细胞中显著降低3.2倍。得出结论，ALS的R528 H突变导致电生理特性的微小差异，但显著降低了全细胞Ca通道电流的幅度。
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 al subunit (alpha(1S)). Here,,ve 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 of als results in minor differences in the electrophysiological properties but significantly reduces the whole-cell Ca channel current in its amplitude.