Ca_v1.1

Cav1.1
已知的結構
PDB	直系同源搜尋: PDBe RCSB
PDBID列表
	2VAY
識別號
別名	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
	地爾硫䓬、維拉帕米、硝苯地平、(3RS,4′RS)-benidipine、拉西地平、bepridil hydrochloride monohydrate、diltiazem hydrochloride、amlodipine besylate
基因位置（人類）
染色體	1號染色體
終止	201,112,451 bp
基因位置（小鼠）
染色體	小鼠1號染色體
終止	136,047,560 bp
RNA表現模式
	查閱更多表現資料
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; • 血漿蛋白結合; • calmodulin binding;
細胞組分	• 細胞質; • 電壓依賴性鈣離子通道; • integral component of membrane; • 膜; • I band; • 橫小管; • L-type voltage-gated calcium channel complex; • 細胞膜; • 肌膜;
生物學過程	• 肌肉收縮; • 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
	779
	12292
	ENSG00000081248
	ENSMUSG00000026407
	Q13698
	Q02789
	NM_000069
	NM_001081023; NM_014193
	NP_000060
	NP_001074492; NP_055008; NP_001389878
	維基資料
檢視/編輯人類	檢視/編輯小鼠

Ca_v1.1又稱為L型鈣離子通道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^[7]。有時又稱CACNL1A3或二氫吡啶（英語：dihydropyridine）受體（dihydropyridine receptor，DHPR）。

功能

該蛋白為骨骼肌中L型電性鈣離子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（英語：hypokalemic periodic paralysis）、甲狀腺毒性週期性麻痺症，和惡性高熱相關^[7]。

Ca_v1.1為骨骼肌橫小管上的電壓依賴性鈣離子通道（英語：voltage-dependent calcium channel）。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（英語：end-plate potential）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離子通道開啟，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^[8]。

臨床意義

在許多低鉀血周期性麻痺（英語：hypokalemic periodic paralysis）（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靜息電位，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（英語：hyperkalemic periodic paralysis）^[9]。

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^[10]。

阻斷劑

Ca_v1.1可由二羥基吡啶（英語：dihydropyridine）阻斷。

參見

鈣離子通道

參考文獻

^ 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. （原始內容存檔於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]. （原始內容存檔於2016-03-21）（英語）.

延伸閱讀

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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.

外部連結

Cav1.1引用了美國國家醫學圖書館提供的資料，這些資料屬於公共領域。

[1] 與Cav1.1相關的疾病；在維基數據上查看/編輯參考.

[2] 對Cav1.1起作用的藥物；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-3] 3.0 ^3.1 ^3.2 GRCh38: Ensembl release 89: ENSG00000081248 - Ensembl, May 2017

[refGRCm38Ensembl-4] 4.0 ^4.1 ^4.2 GRCm38: Ensembl release 89: ENSMUSG00000026407 - Ensembl, May 2017

[5] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[6] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-7] 7.0 ^7.1 Entrez Gene: CACNA1S calcium channel, voltage-dependent, L type, alpha 1S subunit. （原始內容存檔於2010-12-05）.

[pmid11726651-8] 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.

[pmid16075040-9] 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.

[EMHG's_list_of_causative_mutations-10] European Malignant Hyperthermia Group: Mutations in RYR1. emhg.org. [2017-07-07]. （原始內容存檔於2016-03-21）（英語）.

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