CO2‐dependent opening of connexin 26 and related β connexins

CO2‐dependent opening of connexin 26 and related β connexins
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连接蛋白 26 和相关 β 连接蛋白的 CO2 依赖性开放

DOI:
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发表时间:
2010
期刊:
Journal of Physiology
影响因子:
--
通讯作者:
N. Dale
N. Dale
中科院分区:
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文献类型:
--
作者:
Robert T. R. Huckstepp;R. Eason;Anshu Sachdev;N. Dale

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我们之前已经证明了连接蛋白介导的CO2依赖的ATP从延髓表面释放。鉴于连接蛋白26(Cx26)定位于延髓的化学敏感区,我们已经在异源表达系统(HeLa细胞)中测试了Cx26是否对Cx26的变化敏感。Cx26对恒定胞外pH的升高以开放的方式反应,对以关闭的方式减少的反应。此外,Cx26在大约40毫米汞柱的生理压力下被部分激活。孤立斑块中的Cx26对中的变化做出了响应,这表明半通道对二氧化碳的直接敏感性。Cx26在HeLa细胞中的异源表达足以使其具有对CO2敏感的释放ATP的能力。我们已经研究了其他异源表达的连接蛋白对变化的反应能力。与Cx26密切相关的β连接蛋白Cx30和Cx32也表现出对Cx26变化的敏感性,但其特征略有不同。距离较远的Cx43表现出CO2依赖的闭合(可能通过细胞内酸化),而Cx36表现出对CO2的不敏感。这些令人惊讶的发现表明,连接蛋白可能发挥着迄今为止尚未被认识的各种信号作用,而Cx26和相关的β连接蛋白可能在整个大脑中直接传递对二氧化碳的敏感性。
We have previously shown connexin mediated CO2‐dependent ATP release from the surface of the medulla oblongata. Given the localization of connexin 26 (Cx26) to the chemosensing areas of the medulla, we have tested in a heterologous expression system (HeLa cells) whether Cx26 may be sensitive to changes in . Cx26 responded to an increase in at constant extracellular pH by opening and to a decrease in by closing. Furthermore, Cx26 was partially activated at a physiological of around 40 mmHg. Cx26 in isolated patches responded to changes in , suggesting direct CO2 sensitivity of the hemichannel to CO2. Heterologous expression of Cx26 in HeLa cells was sufficient to endow them with the capacity to release ATP in a CO2‐sensitive manner. We have examined other heterologously expressed connexins for their ability to respond to changes in . The closely related β connexins Cx30 and Cx32 also displayed sensitivity to changes in , but with slightly different characteristics from Cx26. The more distant Cx43 exhibited CO2‐dependent closing (possibly mediated through intracellular acidification), while Cx36 displayed no CO2 sensitivity. These surprising findings suggest that connexins may play a hitherto unappreciated variety of signalling roles, and that Cx26 and related β connexins may impart direct sensitivity to CO2 throughout the brain.
DOI: 10.1152/ajpcell.00054.2009
发表时间: 2009-06
期刊: American journal of physiology. Cell physiology
影响因子: --
作者:
M. Retamal;Shengyong Yin;G. Altenberg;L. Reuss
通讯作者: M. Retamal;Shengyong Yin;G. Altenberg;L. Reuss
人连接蛋白26和连接蛋白30形成功能性异聚和异型通道。
DOI: 10.1152/ajpcell.00011.2007
发表时间: 2007
期刊: American journal of physiology. Cell physiology
影响因子: --
作者:
Yum,SabrinaW;Zhang,Junxian;Valiunas,Virginijus;Kanaporis,Giedrius;Brink,PeterR;White,ThomasW;Scherer,StevenS
通讯作者: Scherer,StevenS