Ca2+ responses in enteric glia are mediated by connexin-43 hemichannels and modulate colonic transit in mice.
Ca2+ responses in enteric glia are mediated by connexin-43 hemichannels and modulate colonic transit in mice.
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DOI：
10.1053/j.gastro.2013.10.061
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发表时间：
2014-02
期刊：
影响因子：
29.4
通讯作者：
Gulbransen BD
中科院分区：
文献类型：
--
作者：
McClain J;Grubišić V;Fried D;Gomez-Suarez RA;Leinninger GM;Sévigny J;Parpura V;Gulbransen BD
在肠道神经系统中，神经递质启动神经胶质细胞内钙离子(钙反应)的变化，但这一过程如何影响肠道功能尚不清楚。我们研究了肠神经胶质细胞中钙离子介导的反应是否需要维持胃肠功能。我们使用原位钙成像来监测神经胶质细胞的钙反应，这些反应是通过药物或通过胶质细胞特异性破坏连接蛋白43(Cx43)基因(hGFAP：：creERT2+/−/Cx43f/f小鼠)来操纵的。胃肠功能评估的基础上，小球输出，总肠道通过，结肠排珠，和肌肉张力记录。通过免疫组织化学、免疫印迹和逆转录聚合酶链式反应分析对蛋白质进行定位和定量。小鼠肠神经胶质细胞的钙反应是由Cx43半通道介导的。Cx43免疫反应局限于小鼠结肠肌间神经丛内的肠神经胶质细胞；Cx43抑制剂Carbenoxolone和43Gap26抑制肠神经胶质细胞传播钙反应的能力。在体内，肠神经胶质网络中钙离子反应的减弱减缓了肠道整体的传输速度，并延迟了结肠传输--这些变化在正常衰老过程中也可以观察到。随着年龄的增长，运动性改变与胶质细胞钙离子介导的反应减少以及Cx43基因和蛋白表达的变化有关。肠神经胶质细胞内钙离子介导的反应调节小鼠的胃肠功能。肠神经胶质细胞和神经元之间细胞间信号的改变可能导致运动障碍。
In the enteric nervous system, neurotransmitters initiate changes in Ca2+ (Ca2+ responses) in glia, but it is not clear how this process affects intestinal function. We investigated whether Ca2+-mediated responses in enteric glial are required to maintain gastrointestinal function. We used in situ Ca2+ imaging to monitor glial Ca2+ responses, which were manipulated with pharmacologic agents or via glia-specific disruption of the gene encoding connexin-43 (Cx43) (hGFAP::creERT2+/−/Cx43f/f mice). Gastrointestinal function was assessed based on pellet output, total gut transit, colonic bead expulsion, and muscle tension recordings. Proteins were localized and quantified by immunohistochemistry, immunoblot, and reverse transcription PCR analyses. Ca2+ responses in enteric glia of mice were mediated by Cx43 hemichannels. Cx43 immunoreactivity was confined to enteric glia within the myenteric plexus of the mouse colon; the Cx43 inhibitors carbenoxolone and 43Gap26 inhibited the ability of enteric glia to propagate Ca2+ responses. In vivo attenuation of Ca2+ responses in the enteric glial network slowed gut transit overall and delayed colonic transit—these changes are also observed during normal aging. Altered motility with increasing age was associated with reduced glial Ca2+-mediated responses and changes in glial expression of Cx43 mRNA and protein. Ca2+-mediated responses in enteric glia regulate gastrointestinal function in mice. Altered intercellular signaling between enteric glia and neurons might contribute to motility disorders.
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影响因子：
3.7
作者：
Biagi E;Nylund L;Candela M;Ostan R;Bucci L;Pini E;Nikkïla J;Monti D;Satokari R;Franceschi C;Brigidi P;De Vos W
通讯作者：
De Vos W
DOI：
10.1073/pnas.95.26.15735
发表时间：
1998-12-22
影响因子：
11.1
作者：
Cotrina, ML;Lin, JHC;Nedergaard, M
通讯作者：
Nedergaard, M
影响因子：
6.2
作者：
Koulakoff, Annette;Ezan, Pascal;Giaume, Christian
通讯作者：
Giaume, Christian
影响因子：
3.5
作者：
Gomes, P.;Chevalier, J.;Vanden Berghe, P.
通讯作者：
Vanden Berghe, P.
影响因子：
6.2
作者：
Gangoso, Ester;Ezan, Pascal;Tabernero, Arantxa
通讯作者：
Tabernero, Arantxa