Molecular pathophysiology of voltage-gated ion channels.
Molecular pathophysiology of voltage-gated ion channels.
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电压门控离子通道的分子病理生理学。
DOI：
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
R. Rüdel
中科院分区：
文献类型：
--
作者：
F. Lehmann‐Horn;R. Rüdel
除了阐明一整组遗传性疾病的病理学之外，对这些突变在整个系统（患者）、器官和细胞（切除的肌肉标本）以及通道蛋白水平上的后果的研究告诉我们，我们目前对通道结构-功能关系的看法还远远不够全面。例如，已经假设在钾通道中，以及在钠和钙通道蛋白中，S4单元主要负责通道激活。这一概念必须得到纠正，因为发现重复序列IV的S4突变主要影响通道失活。此外，影响其他通道结构域的突变，如interlinker或其他膜内亚基，不仅在用膜片钳的有限探针测试时，而且在患者水平上也会引起几乎相同的改变。在基因的其他部分，特别是那些编码钠或钙通道的基因中缺乏突变，可能表明相应蛋白质结构域的适当功能对生命至关重要。因此，从自然实验中获得的知识，因为这些疾病可能被细胞生物学家所关注，为定点诱变的结果提供了有价值的补充。为了最终了解疾病的病理学，例如，触发冷或钾的影响，似乎蛋白质回归到细胞甚至全身水平是不可避免的。
In addition to the clarification of the pathology of a whole group of hereditary diseases, the study of the consequences of these mutations at the levels of the whole system (patient), organ and cells (excised muscle specimens), and of the channel proteins has taught us that our current opinions on channel structure-function relations are far from being comprehensive. For instance it had been assumed that as in the potassium channel, also in the sodium and calcium channel proteins, the S4 unit is mainly responsible for channel activation. This notion has to be corrected as mutations in S4 of repeat IV were found to affect mainly channel inactivation. Moreover mutations affecting other channel domains, such as interlinkers or other intramembraneous subunits cause virtually the same alterations, not only when tested with the limited probe of the patch clamp but also on the level of the patient. The lack of mutations in other parts of the genes, in particular those coding for sodium or calcium channels, may indicate that proper function of the corresponding protein domains is essential for life. Thus the knowledge derived from the experiments of Nature, as these diseases may be looked upon by the cell biologist, provides a valuable addition to the results from site-directed mutagenesis. For a final understanding of the pathology of the diseases, for example, triggering effects of cold or potassium, it seems that the regression from the proteins back to the cellular or even systemic levels is unavoidable.
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在成人骨骼肌、心脏和大脑中表达的电压门控 Na 通道 β1 亚基 mRNA 由单个基因编码。
DOI：
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发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Makita,N;BennettJr,PB;GeorgeJr,AL
通讯作者：
GeorgeJr,AL
Xp22.3 区域的一个基因与电压门控氯离子通道具有同源性。
影响因子：
3.5
作者：
vanSlegtenhorst,MA;Bassi,MT;Borsani,G;Wapenaar,MC;Ferrero,GB;deConciliis,L;Rugarli,EI;Grillo,A;Franco,B;Zoghbi,HY;Ballabio,A
通讯作者：
Ballabio,A
DOI：
10.1073/pnas.88.23.10778
发表时间：
1991-12-01
影响因子：
11.1
作者：
DEJONGH, KS;WARNER, C;CATTERALL, WA
通讯作者：
CATTERALL, WA
DOI：
10.1016/s0021-9258(18)54728-1
发表时间：
1991-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
X. Wei;E. Perez-Reyes;A. E. Lacerda;G. Schuster;A. Brown;L. Birnbaumer
通讯作者：
X. Wei;E. Perez-Reyes;A. E. Lacerda;G. Schuster;A. Brown;L. Birnbaumer
大鼠大脑钠通道的石房蛤毒素受体。
DOI：
--
发表时间：
1982
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hartshorne,RP;Messner,DJ;Coppersmith,JC;Catterall,WA
通讯作者：
Catterall,WA