A global defect in scaling relationship between electrical activity and availability of muscle sodium channels in hyperkalemic periodic paralysis
A global defect in scaling relationship between electrical activity and availability of muscle sodium channels in hyperkalemic periodic paralysis
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DOI：
10.1007/s004240050900
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发表时间：
1999-07-01
影响因子：
4.5
通讯作者：
Marom, S
中科院分区：
文献类型：
--
作者：
Melamed-Frank, M;Marom, S
高钾性周期性麻痹（HyperPP）是一种遗传性疾病，其特征是肌无力和肌强直交替发作。与HyperPP相关的最常见突变是肌肉钠通道中的T704 M置换。该突变增加钠持续电流，改变激活的电压依赖性并损害缓慢失活。本研究显示了实验证据，支持T704 M突变引起的潜在重要的全局缺陷。虽然在正常和突变通道中，从缓慢失活恢复的有效速率与过去活动的持续时间相关，但突变通道的缩放能力明显更大。通道之间的这种差异为解释广泛的时间尺度、病史依赖性和混合性肌强直/麻痹效应提供了线索，这些效应标志着HyperPP的临床表现。
Hyperkalemic periodic paralysis (HyperPP) is a hereditary disorder characterized by alternate episodic attacks of muscle weakness and muscle myotonia. The most common mutation associated with HyperPP is a T704M substitution in the skeletal-muscle sodium channel. This mutation increases sodium persistent currents, alters voltage dependence of activation and impairs slow inactivation. The present study shows experimental evidence in support of a potentially important global defect caused by the T704M mutation. While the effective rate of recovery from slow inactivation, in both normal and mutated channels, is related to the duration of past activity by a power law function, the scaling power of the mutated channel is significantly greater. This difference between the channels offers a clue for an explanation to the wide range of time scales, history dependence, and the mixed myotonic/paralysis effect, which mark the clinical picture of HyperPP.