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Cav2.1, also called the P/Qvoltage-dependent calcium channel, is a calcium channel found mainly in the brain.[5] Specifically, it is found on the presynaptic terminals of neurons in the brain and cerebellum.[5] Cav2.1 plays an important role in controlling the release of neurotransmitters between neurons.[5] It is composed of multiple subunits, including alpha-1, beta, alpha-2/delta, and gamma subunits.[6] The alpha-1 subunit is the pore-forming subunit, meaning that the calcium ions flow through it.[6] Different kinds of calcium channels have different isoforms (versions) of the alpha-1 subunit. Cav2.1 has the alpha-1A subunit,[6] which is encoded by the CACNA1A gene.[a][5] Mutations in CACNA1A have been associated with various neurologic disorders, including familial hemiplegic migraine, episodic ataxia type 2, and spinocerebellar ataxia type 6.[5]
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What are CACNA1A-related disorders? (subtitles available!)
Voltage Gated Calcium Channels Part 1
Transcription
Function
"Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas, the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1A subunit, which is predominantly expressed in neuronal tissue."[6]
Clinical significance
Mutations in the CACNA1A gene are associated with multiple neurologic disorders, many of which are episodic, such as familial hemiplegic migraine, movement disorders such as episodic ataxia, and epilepsy with multiple seizure types.[8]
"This gene also exhibits polymorphic variation due to (CAG)n-repeats. Multiple transcript variants encoding different isoforms have been found for this gene. In one set of transcript variants, the (CAG)n-repeats occur in the 3' UTR, and are not associated with any disease. However, in another set of variants, an insertion extends the coding region to include the (CAG)n-repeats which encode a polyglutamine tract. Expansion of the (CAG)n-repeats from the normal 4-16 to 21-28 in the coding region is associated with spinocerebellar ataxia 6."[6]
^"CACNA1A is an abbreviation of the gene's full name, CAlcium voltage-gated ChaNnel subunit AIpha 1A, which is a description of the protein coded for by the gene."[7]
Joutel A, Bousser MG, Biousse V, Labauge P, Chabriat H, Nibbio A, et al. (September 1993). "A gene for familial hemiplegic migraine maps to chromosome 19". Nature Genetics. 5 (1): 40–5. doi:10.1038/ng0993-40. PMID8220421. S2CID6493091.
Margolis RL, Breschel TS, Li SH, Kidwai AS, Antonarakis SE, McInnis MG, Ross CA (July 1995). "Characterization of cDNA clones containing CCA trinucleotide repeats derived from human brain". Somatic Cell and Molecular Genetics. 21 (4): 279–84. doi:10.1007/BF02255782. PMID8525433. S2CID22174220.
Diriong S, Lory P, Williams ME, Ellis SB, Harpold MM, Taviaux S (December 1995). "Chromosomal localization of the human genes for alpha 1A, alpha 1B, and alpha 1E voltage-dependent Ca2+ channel subunits". Genomics. 30 (3): 605–9. doi:10.1006/geno.1995.1284. PMID8825650.
Ophoff RA, Terwindt GM, Vergouwe MN, van Eijk R, Oefner PJ, Hoffman SM, et al. (November 1996). "Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4". Cell. 87 (3): 543–52. doi:10.1016/S0092-8674(00)81373-2. hdl:1765/57576. PMID8898206. S2CID16840573.
Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton DW, Amos C, et al. (January 1997). "Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel". Nature Genetics. 15 (1): 62–9. doi:10.1038/ng0197-62. PMID8988170. S2CID9116828.
Spacey, Sian (December 2011). "Episodic Ataxia Type 2 – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY". Episodic Ataxia Type 2. University of Washington, Seattle. PMID20301674. NBK1501. In GeneReviews
This page was last edited on 28 January 2024, at 03:28