Report

Astrocytes Control Breathing Through pH-Dependent Release of ATP

Science  15 Jul 2010:

DOI: 10.1126/science.1190721

Abstract

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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