Human Na+ channel fast and slow inactivation in paramyotonia congenita mutants expressed in Xenopus laevis oocytes.
Human Na+ channel fast and slow inactivation in paramyotonia congenita mutants expressed in Xenopus laevis oocytes.
复制标题
非洲爪蟾卵母细胞中表达的先天性副肌强直突变体中人钠离子通道快速和缓慢失活。
DOI：
10.1113/jphysiol.1997.sp021952
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Ruben,PC
中科院分区：
文献类型：
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作者：
Richmond,JE;Featherstone,DE;Ruben,PC
1.先天性副肌强直（Paramyotonia congenita，PC）是一种由骨骼肌钠通道中一个或多个氨基酸取代引起的人类遗传性疾病。使用macropatches，将PC突变R1448 C和T1313 M与野生型（WT）在与人骨骼肌（SkM 1）钠通道α和β亚基共注射的非洲爪蟾卵母细胞中的作用进行了比较。2. T1313 M或R1448 C中的缓慢失活与WT没有差异。快速失活在两个PC突变体，但是，显着改变。3.常用的生物物理方案（如I-V曲线、稳态失活曲线和失活率的测量）并不一致地表明过度兴奋应该由T1313 M或R1448 C引起。事实上，与WT相比，T1313 M和R1448 C共同的预测细胞过度兴奋的快速失活的唯一改变是缓慢的开放状态失活。4.为了测试这种改变是否足以引起表型过度兴奋，我们使用了一种模拟肌肉膜活动的新电压命令。使用该协议，我们发现R1448 C和T1313 M是相似的，因为与WT相比，它们在高频活动期间保持显著更高的信道可用性。
1. Paramyotonia congenita (PC) is a human hereditary disease caused by one or more amino acid substitutions in skeletal muscle sodium channels. Using macropatches, the effect of PC mutations R1448C and T1313M were compared with wild‐type (WT) in Xenopus oocytes coinjected with both alpha‐ and beta‐subunits of human skeletal muscle (SkM1) sodium channels. 2. Slow inactivation in either T1313M or R1448C was not different from WT. Fast inactivation in both PC mutants, however, was significantly altered. 3. Commonly used biophysical protocols (such as I‐V curves, steady‐state inactivation curves, and measurements of inactivation rates) did not uniformly indicate that hyperexcitability should result from T1313M or R1448C. In fact, the only alteration of fast inactivation common to T1313M and R1448C that predicted cellular hyperexcitability was slowed open‐state inactivation, compared with WT. 4. To test whether this alteration was sufficient to cause the phenotypic hyperexcitability, we used a novel voltage command that simulated muscle membrane activity. With this protocol, we found that R1448C and T1313M were similar in that they maintained a significantly higher channel availability during high frequency activity, compared with WT.