Astrocytes control breathing through pH-dependent release of ATP.

Astrocytes control breathing through pH-dependent release of ATP.
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DOI:
10.1126/science.1190721
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发表时间:
2010-07-30
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Kasparov S
Kasparov S
中科院分区:
其他
文献类型:
--
作者:
Gourine AV;Kasymov V;Marina N;Tang F;Figueiredo MF;Lane S;Teschemacher AG;Spyer KM;Deisseroth K;Kasparov S

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星形胶质细胞为神经元网络提供结构和代谢支持,但证明其在复杂行为中发挥积极作用的直接证据有限。中枢呼吸系统药物敏感性是一种重要的机制,通过调节呼吸,维持血液和脑内PCO2/pH的恒定水平。我们发现脑干化学感受器区域的星形胶质细胞对化学药物高度敏感。它们对生理性的pH下降作出反应,细胞内钙离子和ATP的释放显著增加。ATP促进星形胶质细胞钙离子兴奋,激活化学感受器神经元,并诱导呼吸的适应性增加。通过光发生刺激表达通道视紫红质-2的星形胶质细胞,模拟pH引起的钙离子反应,通过ATP依赖的机制激活化学感受器神经元,并在体内触发强大的呼吸反应。这证明了大脑神经胶质细胞在调节基本的生理反射方面可能起着至关重要的作用。
Astrocytes provide structural and metabolic support for neuronal networks, but direct evidence demonstrating their active role in complex behaviors is limited. Central respiratory chemosensitivity is an essential mechanism which, via regulation of breathing, maintains constant levels of blood and brain PCO2/pH. We found that astrocytes of the brainstem chemoreceptor areas are highly chemosensitive. They responded to physiological decreases in pH with vigorous elevations in intracellular Ca2+ and release of ATP. ATP propagated astrocytic Ca2+ excitation, activated chemoreceptor neurons, and induced adaptive increases in breathing. Mimicking pH-evoked Ca2+ responses by optogenetic stimulation of astrocytes expressing channelrhodopsin-2 activated chemoreceptor neurons via ATP-dependent mechanism and triggered robust respiratory responses in vivo. This demonstrates a potentially crucial role for brain glial cells in mediating a fundamental physiological reflex.
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