Episodic ataxia results from voltage-dependent potassium channels with altered functions
Episodic ataxia results from voltage-dependent potassium channels with altered functions
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DOI：
10.1016/0896-6273(95)90022-5
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发表时间：
1995-12-01
期刊：
影响因子：
16.2
通讯作者：
Maylie, J
中科院分区：
文献类型：
--
作者：
Adelman, JP;Bond, CT;Maylie, J
发作性共济失调（Episodic ataxia，EA）是一种常染色体显性遗传疾病，可引起持续性肌震颤和全身性共济失调。最近，家族性EA已与12号染色体上的电压依赖性延迟整流器Kv1.1有关。已经确定了六个EA家族携带不同的Kv1.1错义突变，所有个体都是杂合子。在非洲爪蟾卵母细胞中的表达表明，两个EA亚基形成具有改变的门控特性的同源通道。V408A通道具有与野生型通道相似的电压依赖性，但具有更快的动力学和增加的C型失活，而F184C通道的电压依赖性正移20 mV。其他四个EA亚基不产生功能的同源性通道，但减少钾电流时，与野生型亚基共组装。结果表明，在EA的细胞机制，其中受影响的神经细胞不能有效地恢复后，动作电位，因为改变了延迟整流功能。
Episodic ataxia (EA) is an autosomal dominant human disorder that produces persistent myokymia and attacks of generalized ataxia. Recently, familial EA has been linked to the voltage-dependent delayed rectifier, Kv1.1, on chromosome 12. Six EA families have been identified that carry distinct Kv1.1 missense mutations; all individuals are heterozygous. Expression in Xenopus oocytes demonstrates that two of the EA subunits form homomeric channels with altered gating properties. V408A channels have voltage dependence similar to that bf wild-type channels, but with faster kinetics and increased C-type inactivation, while the voltage dependence of F184C channels is shifted 20 mV positive. The other four EA subunits do not produce functional homomeric channels but reduce the potassium current when coassembled with wild-type subunits. The results suggest a cellular mechanism underlying EA in which the affected nerve cells cannot efficiently repolarize following an action potential because of altered delayed rectifier function.