Implication of the C-terminal region of the α-subunit of voltage-gated sodium channels in fast inactivation
Implication of the C-terminal region of the α-subunit of voltage-gated sodium channels in fast inactivation
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DOI：
10.1007/s00232-001-0058-5
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发表时间：
2001-09-15
影响因子：
2.4
通讯作者：
Chahine, M
中科院分区：
文献类型：
--
作者：
Deschênes, I;Trottier, E;Chahine, M
人类心脏 (hH1) 和人类骨骼肌 (hSkM1) 钠通道的 α 亚基均在哺乳动物表达系统中表达。这些通道显示出与天然组织中相似的慢速 (hH1) 和快速 (hSkM1) 电流衰减动力学。因此，本研究的目的是确定 α 亚基上与这些电流衰变动力学差异有关的区域。构建了一系列 hH1/hSkM1 嵌合钠通道，重点关注 C 端区域。使用膜片钳技术在全细胞配置中记录嵌合通道的钠电流，其中hH1和hSkM1之间交换了C末端区域的嵌合体表明该区域包含导致这些钠通道亚型之间的电流衰减动力学差异的元素。其他生物物理特征（稳态激活和失活以及从失活中恢复）与亲本通道的表型相似。这表明 C 末端仅与当前衰变动力学的差异有关。构建了其他几个嵌合体来鉴定导致这种差异的 C 末端的特定区域。我们的结果表明，C 末端区域的前 100 个氨基酸片段含有可能导致心脏和骨骼肌钠通道之间电流衰减差异的成分。
The alpha -subunit of both the human heart (hH1) and human skeletal muscle (hSkM1) sodium channels were expressed in a mammalian expression system. The channels displayed slow (hH1) and fast (hSkM1) current decay kinetics similar to those seen in native tissues. Hence, the aim of this study was to identify the region on the alpha -subunit involved in the differences of these current-decay kinetics. A series of hH1/hSkM1 chimeric sodium channels were constructed with the focus on the C-terminal region. Sodium currents of chimeric channels were recorded using the patch-clamp technique in whole-cell configuration, Chimeras where the C-terminal region had been exchanged between hH1 and hSkM1 revealed that this region contains the elements that cause differences in current decay kinetics between these sodium channel isoforms. Other biophysical characteristics (steady-state activation and inactivation and recovery from inactivation) were similar to the phenotype of the parent channel. This indicates that the C-terminus is exclusively implicated in the differences of current decay kinetics. Several other chimeras were constructed to identify a specific region of the C-terminus causing this difference. Our results showed that the first 100-amino-acid stretch of the C-terminal region contains constituents that could cause the differences in current decay between the heart and skeletal muscle sodium channels.