Cloning, expression, and distribution of a Ca2+-activated K+ channel beta-subunit from human brain

Cloning, expression, and distribution of a Ca2+-activated K+ channel beta-subunit from human brain
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DOI:
10.1073/pnas.93.17.9200
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发表时间:
1996-08-20
影响因子:
11.1
通讯作者:
Reinhart, PH
Reinhart, PH
中科院分区:
综合性期刊1区
文献类型:
--
作者:
TsengCrank, J;Godinot, N;Reinhart, PH

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我们从人脑中克隆并表达了一个Ca ~(2+)激活的K ~+通道β亚基,其开放阅读框架编码一个191个氨基酸的蛋白,与先前从牛肌肉中克隆的一个亚基具有显著的同源性。该亚基的基因位于5号染色体上的q34带没有证据表明该基因产物的可变RNA剪接,hslo-β mRNA在平滑肌中大量表达,但在大多数其他组织中表达水平较低,包括脑。β亚基mRNA表达相对较高的脑亚区是海马和胼胝体,hslo-β mRNA与hslo-α亚基在非洲爪蟾卵母细胞或稳定转染的HEK 293细胞中的共表达引起了钙激活的钾电流,其钙和/或电压敏感性大大增加。这些数据表明,β亚基显示出与α亚基不同的组织分布,在许多组织中,α亚基与β亚基之间可能没有关联。这些β亚基可以通过调节α亚基的Ca ~(2+)和/或电压依赖性,在神经元兴奋性的调节中发挥功能性作用。
We have cloned and expressed a Ca2+-activated K+ channel beta-subunit from human brain, The open reading frame encodes a 191-amino acid protein possessing significant homology to a previously described subunit cloned from bovine muscle. The gene for this subunit is located on chromosome 5 at band q34 (hslo-beta), There is no evidence for alternative RNA splicing of this gene product, hslo-beta mRNA is abundantly expressed in smooth muscle, but expression levels are low in most other tissues, including brain, Brain subregions in which beta-subunit mRNA expression is relatively high are the hippocampus and corpus callosum, The coexpression of hslo-beta mRNA together with hslo-alpha subunits in either Xenopus oocytes or stably transfected HEK 293 cells gives rise to Ca2+-activated potassium currents with a much increased calcium and/or voltage sensitivity, These data indicate that the beta-subunit shows a tissue distribution different to that of the alpha-subunit, and in many tissues there may be no association of alpha-subunits with beta-subunits, These beta-subunits can play a functional role in the regulation of neuronal excitability by tuning the Ca2+ and/or the voltage dependence of alpha-subunits.