Cav1.1

Cav1.1
已知的結構 PDB 直系同源搜索: PDBe RCSB PDBID列表 2VAY
識別號
别名	CACNA1S；, CACNL1A3, CCHL1A3, Cav1.1, HOKPP, HOKPP1, MHS5, TTPP1, hypoPP, calcium voltage-gated channel subunit alpha1 S, DHPR
外部ID	OMIM：114208 MGI：88294 HomoloGene：37257 GeneCards：CACNA1S
相關疾病
低血鉀性週期性麻痺症
為以下藥物的標靶
地尔硫䓬、​维拉帕米、​硝苯地平、​(3RS,4′RS)-benidipine、​拉西地平、​bepridil hydrochloride monohydrate、​diltiazem hydrochloride、​amlodipine besylate
基因位置（人类） 染色体 1號染色體 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
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基因本體 分子功能 • voltage-gated calcium channel activity • calcium channel activity • 金屬離子結合 • voltage-gated ion channel activity • high voltage-gated calcium channel activity • ion channel activity • 血浆蛋白结合 • calmodulin binding 細胞組分 • 細胞質 • 電壓依賴性鈣通道 • integral component of membrane • 膜 • I band • 横小管 • L-type voltage-gated calcium channel complex • 细胞膜 • 肌膜 生物學過程 • 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 Sources:Amigo / QuickGO
直系同源
物種	人類	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​（UCSC）	Chr 1: 201.04 – 201.11 Mb	Chr 1: 135.98 – 136.05 Mb
PubMed​查找
維基數據
檢視/編輯人類 檢視/編輯小鼠

Ca_v1.1又稱為L型鈣通道α1亞基（calcium channel, voltage-dependent, L type, alpha 1S subunit，CACNA1S），為一種由CACNA1S基因轉譯而成的蛋白質。有時又稱CACNL1A3或二氫吡啶受體（dihydropyridine receptor，DHPR）。

功能

該蛋白為骨骼肌中L型電性鈣通道的五個次單元中的其中之一。該基因突變可能與低鉀血周期性麻痺、甲狀腺毒性週期性麻痺症，和惡性高熱相關。

Ca_v1.1為骨骼肌横小管上的電壓依賴性鈣通道。在骨骼肌中會與肌漿網上的蘭諾定受體1（RyR1）相接。當神經衝動發生時，終板電位會沿骨骼肌的細胞膜傳入橫小管中，並刺激Ca_v1.1。先前科學家以為當肌肉去極化時會引發鈣通道開啟，鈣離子流入後活化RyR1，使更多鈣離子從肌漿網釋入細胞質，引發興奮收縮聯合作用，進而使肌肉收縮。最近研究發現在骨骼肌中（並非心肌），鈣離子流入Cav1.1並非必須。Cav1.1活化後構型會改變，並與RyR1相接進行別構調節。

臨床意義

在許多低鉀血周期性麻痺（HOKPP）患者身上，Ca_v1.1的 domains 2 和 domains 4 有突變發生，造成其感測去極化的能力下降，活化蘭諾定受體的能力下降。因此肌肉無法順利收縮，導致患者癱瘓。此類患者會於低血鉀時發生癱瘓，因胞外血鉀降低會使肌肉更快回到静息电位，且會使電位更難達到閾值，使動作電位更難產生，肌肉因此無力。在Ca_v1.1缺損的患者身上，即使動作電位產生，肌漿網仍難以釋放鈣離子，使肌肉收縮無法完成，因此此類患者必須調整血鉀濃度。相反地，若鈉離子通道突變後功能增強，使肌肉長期維持去極化，則會導致高鉀血周期性麻痺。

歐洲惡性高熱小組（European Malignant Hyperthermia Group）將此 CACNA1S 基因的兩種突變列為惡性高熱的診斷之一。

阻斷劑

Ca_v1.1可由二羥基吡啶阻斷。

參見

• 钙通道

延伸閱讀

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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. 
• 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. 
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• 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. 

外部連結

• GeneReviews/NCBI/NIH/UW entry on Malignant Hyperthermia Susceptibility（页面存档备份，存于互联网档案馆）
• 醫學主題詞表（MeSH）：CACNA1S+protein,+human

Cav1.1引用了美国国家医学图书馆提供的資料，这些資料属于公共领域。