Cav1.1
Cav1.1又称为L型钙通道α1亚基（calcium channel, voltage-dependent, L type, alpha 1S subunit，CACNA1S），为一种由CACNA1S基因翻译而成的蛋白质[7]。有时又称CACNL1A3或二氢吡啶受体（dihydropyridine receptor，DHPR）。
功能
该蛋白为骨骼肌中L型电性钙通道的五个次单元中的其中之一。该基因突变可能与低钾血周期性麻痹、甲状腺毒性周期性麻痹症，和恶性高热相关[7]。
Cav1.1为骨骼肌横小管上的电压依赖性钙通道。在骨骼肌中会与肌浆网上的兰诺定受体1（RyR1）相接。当神经冲动发生时，终板电位会沿骨骼肌的细胞膜传入横小管中，并刺激Cav1.1。先前科学家以为当肌肉去极化时会引发钙通道开启，钙离子流入后激活RyR1，使更多钙离子从肌浆网释入细胞质，引发兴奋收缩联合作用，进而使肌肉收缩。最近研究发现在骨骼肌中（并非心肌），钙离子流入Cav1.1并非必须。Cav1.1激活后构型会改变，并与RyR1相接进行别构调节[8]。
临床意义
在许多低钾血周期性麻痹（HOKPP）患者身上，Cav1.1的 domains 2 和 domains 4 有突变发生，造成其感测去极化的能力下降，激活兰诺定受体的能力下降。因此肌肉无法顺利收缩，导致患者瘫痪。此类患者会于低血钾时发生瘫痪，因胞外血钾降低会使肌肉更快回到静息电位，且会使电位更难达到阈值，使动作电位更难产生，肌肉因此无力。在Cav1.1缺损的患者身上，即使动作电位产生，肌浆网仍难以释放钙离子，使肌肉收缩无法完成，因此此类患者必须调整血钾浓度。相反地，若钠离子通道突变后功能增强，使肌肉长期维持去极化，则会导致高钾血周期性麻痹[9]。
欧洲恶性高热小组（European Malignant Hyperthermia Group）将此 CACNA1S 基因的两种突变列为恶性高热的诊断之一[10]。
阻断剂
Cav1.1可由二羟基吡啶阻断。
参见
参考文献
- ^ 與Cav1.1相關的疾病；在維基數據上查看/編輯參考.
- ^ 對Cav1.1起作用的藥物；在維基數據上查看/編輯參考.
- ^ 3.0 3.1 3.2 GRCh38: Ensembl release 89: ENSG00000081248 - Ensembl, May 2017
- ^ 4.0 4.1 4.2 GRCm38: Ensembl release 89: ENSMUSG00000026407 - Ensembl, May 2017
- ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ 7.0 7.1 Entrez Gene: CACNA1S calcium channel, voltage-dependent, L type, alpha 1S subunit. （原始内容存档于2010-12-05）.
- ^ Proenza C, O'Brien J, Nakai J, Mukherjee S, Allen PD, Beam KG. Identification of a region of RyR1 that participates in allosteric coupling with the alpha(1S) (Ca(V)1.1) II-III loop. J. Biol. Chem. February 2002, 277 (8): 6530–5. PMID 11726651. doi:10.1074/jbc.M106471200.
- ^ Jurkat-Rott K, Lehmann-Horn F. Muscle channelopathies and critical points in functional and genetic studies. J. Clin. Invest. August 2005, 115 (8): 2000–9. PMC 1180551
. PMID 16075040. doi:10.1172/JCI25525.
- ^ European Malignant Hyperthermia Group: Mutations in RYR1. emhg.org. [2017-07-07]. （原始内容存档于2016-03-21） （英语）.
延伸阅读
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