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Bradykinin‐induced astrocyte–neuron signalling: glutamate release is mediated by ROS‐activated volume‐sensitive outwardly rectifying anion channels
Author(s) -
Liu HongTao,
Akita Tenpei,
Shimizu Takahiro,
Sabirov Ravshan Z.,
Okada Yasunobu
Publication year - 2009
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2008.165084
Subject(s) - bradykinin , astrocyte , glutamate receptor , chemistry , channel blocker , riluzole , neuron , intracellular , microbiology and biotechnology , biophysics , biochemistry , biology , neuroscience , receptor , central nervous system , calcium , organic chemistry
Glial cells release gliotransmitters which signal to adjacent neurons and glial cells. Previous studies showed that in response to stimulation with bradykinin, glutamate is released from rat astrocytes and causes NMDA receptor‐mediated elevation of intracellular Ca 2+ in adjacent neurons. Here, we investigate how bradykinin‐induced glutamate release from mouse astrocytes signals to neighbouring neurons in co‐cultures. Astrocyte‐to‐neuron signalling and bradykinin‐induced glutamate release from mouse astrocytes were both inhibited by the anion channel blocker 4,4′‐diisothiocyanatostilbene‐2,2′‐disulfonic acid (DIDS) and phloretin. Glutamate release was also sensitive to 4‐(2‐Butyl‐6,7‐dichlor‐2‐cyclopentylindan‐1‐on‐5‐yl) oxybutyric acid (DCPIB), a specific blocker of the volume‐sensitive outwardly rectifying anion channel (VSOR). Astrocytes, but not neurons, responded to bradykinin with activation of whole‐cell Cl − currents. Although astrocytes stimulated with bradykinin did not undergo cell swelling, the bradykinin‐activated current exhibited properties typical of VSOR: outward rectification, inhibition by osmotic shrinkage, sensitivity to DIDS, phloretin and DCPIB, dependence on intracellular ATP, and permeability to glutamate. Bradykinin increased intracellular reactive oxygen species (ROS) in mouse astrocytes. Pretreatment of mouse astrocytes with either a ROS scavenger or an NAD(P)H oxidase inhibitor blocked bradykinin‐induced activation of VSOR, glutamate release and astrocyte‐to‐neuron signalling. By contrast, pretreatment with BAPTA‐AM or tetanus neurotoxin A failed to suppress bradykinin‐induced glutamate release. Thus, VSOR activated by ROS in mouse astrocytes in response to stimulation with bradykinin, serves as the pathway for glutamate release to mediate astrocyte‐to‐neuron signalling. Since bradykinin is an initial mediator of inflammation, VSOR might play a role in glia–neuron communication in the brain during inflammation.