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基因转译而成的蛋白质[7]。有时又称CACNL1A3或二氢吡啶受体（dihydropyridine receptor，DHPR）。
功能
[编辑]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，钙离子流入后活化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活化后构型会改变，并与RyR1相接进行别构调节[8]。
临床意义
[编辑]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，活化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
[编辑]Cav1.1可由二羟基吡啶阻断。
参见
[编辑]参考文献
[编辑]- ^ 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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- Röhrkasten A, Meyer HE, Nastainczyk W, Sieber M, Hofmann F. cAMP-dependent protein kinase rapidly phosphorylates serine- 687 of the skeletal muscle receptor for calcium channel blockers. J. Biol. Chem. 1988, 263 (30): 15325–9. PMID 2844809.
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- Hogan K, Powers PA, Gregg RG. Cloning of the human skeletal muscle alpha 1 subunit of the dihydropyridine-sensitive L-type calcium channel (CACNL1A3). Genomics. 1994, 24 (3): 608–9. PMID 7713519. doi:10.1006/geno.1994.1677.
- Elbaz A, Vale-Santos J, Jurkat-Rott K, Lapie P, Ophoff RA, Bady B, Links TP, Piussan C, Vila A, Monnier N. Hypokalemic periodic paralysis and the dihydropyridine receptor (CACNL1A3): genotype/phenotype correlations for two predominant mutations and evidence for the absence of a founder effect in 16 caucasian families. Am. J. Hum. Genet. 1995, 56 (2): 374–80. PMC 1801148 . PMID 7847370.
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- Ptácek LJ, Tawil R, Griggs RC, Engel AG, Layzer RB, Kwieciński H, McManis PG, Santiago L, Moore M, Fouad G. Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. Cell. 1994, 77 (6): 863–8. PMID 8004673. doi:10.1016/0092-8674(94)90135-X.
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