Cav1.1
Cav1.1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[7]。有時又稱CACNL1A3或二氫吡啶受體（dihydropyridine receptor，DHPR）。
功能
[编辑]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[7]。
Cav1.1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Cav1.1。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[8]。
臨床意義
[编辑]在許多低鉀血周期性麻痺（HOKPP）患者身上，Cav1.1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Cav1.1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[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
[编辑]Cav1.1可由二羥基吡啶阻斷。
參見
[编辑]參考文獻
[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.
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- 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.
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