Astrocytes control breathing through pH-dependent release of ATP.
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 that, via regulation of breathing, maintains constant levels of blood and brain pH and partial pressure of CO2. 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 adenosine triphosphate (ATP). ATP propagated astrocytic Ca2+ excitation, activated chemoreceptor neurons, and induced adaptive increases in breathing. Mimicking pH-evoked Ca2+ responses by means of optogenetic stimulation of astrocytes expressing channelrhodopsin-2 activated chemoreceptor neurons via an 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.
Gourine
Alexander V
AV
Neuroscience, Physiology, and Pharmacology, University College London, London WC1E 6BT, UK. a.gourine@ucl.ac.uk
Kasymov
Vitaliy
V
Marina
Nephtali
N
Tang
Feige
F
Figueiredo
Melina F
MF
Lane
Samantha
S
Teschemacher
Anja G
AG
Spyer
K Michael
KM
Deisseroth
Karl
K
Kasparov
Sergey
S
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001933:Brain Stem / Q000166:cytology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002245:Carbon Dioxide / Q000032:analysis / Q000097:blood; D002478:Cells, Cultured; D002628:Chemoreceptor Cells / Q000502:physiology*; D005089:Exocytosis; D017629:Gap Junctions / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008027:Light; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology*; D008564:Membrane Potentials; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D012119:Respiration; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism
D018048:Receptors, Purinergic P2; D002245:Carbon Dioxide; D000255:Adenosine Triphosphate; D012243:Rhodopsin; D002118:Calcium