Cav1.1

Cav1.1
已知的结构 PDB 直系同源搜索：PDBe RCSB PDBID列表 2VAY
标识符
代号	CACNA1S
扩展标识	OMIM：114208；MGI：88294；HomoloGene：37257；GeneCards：CACNA1S；OMA：CACNA1S - orthologs
基因位置（人类） 染色体 1号染色体 基因座 1q32.1 起始 201,039,512 bp 终止 201,112,451 bp
基因位置（小鼠） 染色体 小鼠1号染色体 基因座 1 E4|1 59.55 cM 起始 135,980,488 bp 终止 136,047,560 bp
RNA表达模式 Bgee 人类 小鼠（直系同源） Top expressed in muscle of thigh Skeletal muscle tissue of rectus abdominis Skeletal muscle tissue of biceps brachii Top expressed in muscle of thigh medial head of gastrocnemius muscle skeletal muscle tissue 查阅更多表达数据 BioGPS 查阅更多表达数据
基因本体 分子功能 voltage-gated calcium channel activity calcium channel activity 金属离子结合 voltage-gated ion channel activity high voltage-gated calcium channel activity ion channel activity 血浆蛋白结合 calmodulin binding 细胞组分 细胞质 电压依赖性钙通道 integral component of membrane 膜 I band 横小管 L-type voltage-gated calcium channel complex 细胞膜 肌膜 生物学过程 肌肉收缩 membrane depolarization during action potential regulation of ion transmembrane transport ion transport calcium ion transmembrane transport transmembrane transport calcium ion transport cellular response to caffeine calcium ion import cardiac conduction 来源：Amigo / QuickGO
直系同源 物种 人类 小鼠 Entrez 779 12292 Ensembl ENSG00000081248 ENSMUSG00000026407 UniProt Q13698 Q02789 mRNA序列 ​NM_000069 NM_001081023 ​NM_014193 蛋白序列 NP_000060 NP_001074492 ​NP_055008 ​NP_001389878 基因位置 Chr 1：201.04 – 201.11 Mb Chr 1：135.98 – 136.05 Mb PubMed查询
维基数据
查看/编辑人类 查看/编辑小鼠

Ca_v1.1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。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。

Ca_v1.1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Ca_v1.1。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。

临床意义

在许多低钾血周期性麻痹（HOKPP）患者身上，Ca_v1.1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Ca_v1.1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。

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。

阻断剂

Ca_v1.1可由二羟基吡啶阻断。

参见

• 钙通道

延伸阅读

• Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J. International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol. Rev. 2005, 57 (4): 411–25. PMID 16382099. doi:10.1124/pr.57.4.5. 
• Rotman EI, De Jongh KS, Florio V, Lai Y, Catterall WA. Specific phosphorylation of a COOH-terminal site on the full-length form of the alpha 1 subunit of the skeletal muscle calcium channel by cAMP-dependent protein kinase. J. Biol. Chem. 1992, 267 (23): 16100–5. PMID 1322891. 
• 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. 
• Tanabe T, Takeshima H, Mikami A, Flockerzi V, Takahashi H, Kangawa K, Kojima M, Matsuo H, Hirose T, Numa S. Primary structure of the receptor for calcium channel blockers from skeletal muscle. Nature. 1987, 328 (6128): 313–8. PMID 3037387. doi:10.1038/328313a0. 
• 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. 
• Boerman RH, Ophoff RA, Links TP, van Eijk R, Sandkuijl LA, Elbaz A, Vale-Santos JE, Wintzen AR, van Deutekom JC, Isles DE. Mutation in DHP receptor alpha 1 subunit (CACLN1A3) gene in a Dutch family with hypokalaemic periodic paralysis. J. Med. Genet. 1995, 32 (1): 44–7. PMC 1050178 . PMID 7897626. doi:10.1136/jmg.32.1.44. 
• Gregg RG, Couch F, Hogan K, Powers PA. Assignment of the human gene for the alpha 1 subunit of the skeletal muscle DHP-sensitive Ca2+ channel (CACNL1A3) to chromosome 1q31-q32. Genomics. 1993, 15 (1): 107–12. PMID 7916735. doi:10.1006/geno.1993.1017. 
• Jurkat-Rott K, Lehmann-Horn F, Elbaz A, Heine R, Gregg RG, Hogan K, Powers PA, Lapie P, Vale-Santos JE, Weissenbach J. A calcium channel mutation causing hypokalemic periodic paralysis. Hum. Mol. Genet. 1994, 3 (8): 1415–9. PMID 7987325. doi:10.1093/hmg/3.8.1415. 
• 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. 
• Drouet B, Garcia L, Simon-Chazottes D, Mattei MG, Guénet JL, Schwartz A, Varadi G, Pinçon-Raymond M. The gene coding for the alpha 1 subunit of the skeletal dihydropyridine receptor (Cchl1a3 = mdg) maps to mouse chromosome 1 and human 1q32. Mamm. Genome. 1993, 4 (9): 499–503. PMID 8118099. doi:10.1007/BF00364784. 
• Iles DE, Segers B, Olde Weghuis D, Suijkerbuijk R, Mikala G, Schwartz A, Wieringa B. Refined localization of the alpha 1-subunit of the skeletal muscle L-type voltage-dependent calcium channel (CACNL1A3) to human chromosome 1q32 by in situ hybridization. Genomics. 1994, 19 (3): 561–3. PMID 8188298. doi:10.1006/geno.1994.1106. 
• O'Brien RO, Taske NL, Hansbro PM, Matthaei KI, Hogan SP, Denborough MA, Foster PS. Exclusion of defects in the skeletal muscle specific regions of the DHPR alpha 1 subunit as frequent causes of malignant hyperthermia. J. Med. Genet. 1995, 32 (11): 913–4. PMC 1051750 . PMID 8592342. doi:10.1136/jmg.32.11.913. 
• Hogan K, Gregg RG, Powers PA. The structure of the gene encoding the human skeletal muscle alpha 1 subunit of the dihydropyridine-sensitive L-type calcium channel (CACNL1A3). Genomics. 1996, 31 (3): 392–4. PMID 8838325. doi:10.1006/geno.1996.0066. 
• Robinson RL, Monnier N, Wolz W, Jung M, Reis A, Nuernberg G, Curran JL, Monsieurs K, Stieglitz P, Heytens L, Fricker R, van Broeckhoven C, Deufel T, Hopkins PM, Lunardi J, Mueller CR. A genome wide search for susceptibility loci in three European malignant hyperthermia pedigrees. Hum. Mol. Genet. 1997, 6 (6): 953–61. PMID 9175745. doi:10.1093/hmg/6.6.953. 
• Monnier N, Procaccio V, Stieglitz P, Lunardi J. Malignant-hyperthermia susceptibility is associated with a mutation of the alpha 1-subunit of the human dihydropyridine-sensitive L-type voltage-dependent calcium-channel receptor in skeletal muscle. Am. J. Hum. Genet. 1997, 60 (6): 1316–25. PMC 1716149 . PMID 9199552. doi:10.1086/515454. 
• Meyers MB, Puri TS, Chien AJ, Gao T, Hsu PH, Hosey MM, Fishman GI. Sorcin associates with the pore-forming subunit of voltage-dependent L-type Ca2+ channels. J. Biol. Chem. 1998, 273 (30): 18930–5. PMID 9668070. doi:10.1074/jbc.273.30.18930. 
• Morrill JA, Brown RH, Cannon SC. Gating of the L-type Ca channel in human skeletal myotubes: an activation defect caused by the hypokalemic periodic paralysis mutation R528H. J. Neurosci. 1998, 18 (24): 10320–34. PMID 9852570. 
• Protasi F, Paolini C, Nakai J, Beam KG, Franzini-Armstrong C, Allen PD. Multiple regions of RyR1 mediate functional and structural interactions with alpha(1S)-dihydropyridine receptors in skeletal muscle. Biophys. J. 2002, 83 (6): 3230–44. PMC 1302400 . PMID 12496092. doi:10.1016/S0006-3495(02)75325-3. 
• Carsana A, Fortunato G, De Sarno C, Brancadoro V, Salvatore F. Identification of new polymorphisms in the CACNA1S gene. Clin. Chem. Lab. Med. 2003, 41 (1): 20–2. PMID 12636044. doi:10.1515/CCLM.2003.004. 

外部链接

• GeneReviews/NCBI/NIH/UW entry on Malignant Hyperthermia Susceptibility（页面存档备份，存于互联网档案馆）
• 医学主题词表（MeSH）：CACNA1S+protein,+human

Cav1.1引用了美国国家医学图书馆提供的数据，这些数据属于公共领域。