title: A novel subtype of astrocytes expressing TRPV4 (transient receptor potential vanilloid 4) regulates neuronal excitability via release of gliotransmitters.
abstract: Astrocytes play active roles in the regulation of synaptic transmission. Neuronal excitation can evoke Ca(2+) transients in astrocytes, and these Ca(2+) transients can modulate neuronal excitability. Although only a subset of astrocytes appears to communicate with neurons, the types of astrocytes that can regulate neuronal excitability are poorly characterized. We found that ∼30% of astrocytes in the brain express transient receptor potential vanilloid 4 (TRPV4), indicating that astrocytic subtypes can be classified on the basis of their expression patterns. When TRPV4(+) astrocytes are activated by ligands such as arachidonic acid, the activation propagates to neighboring astrocytes through gap junctions and by ATP release from the TRPV4(+) astrocytes. After activation, both TRPV4(+) and TRPV4(-) astrocytes release glutamate, which acts as an excitatory gliotransmitter to increase synaptic transmission through type 1 metabotropic glutamate receptor (mGluR). Our results indicate that TRPV4(+) astrocytes constitute a novel subtype of the population and are solely responsible for initiating excitatory gliotransmitter release to enhance synaptic transmission. We propose that TRPV4(+) astrocytes form a core of excitatory glial assembly in the brain and function to efficiently increase neuronal excitation in response to endogenous TRPV4 ligands.
authors.affiliation: From the Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan, shibasaki@gunma-u.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Shibasaki
authors.affiliation: Division of Neurobiology Neuroinformatics, Department of Physiological Sciences, The Graduate University for Advanced Studies, Okazaki 444-8585, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikenaka
authors.affiliation: Department of Physiology, Saitama Medical University, Moroyama 350-0495, Japan.
authors.forename: Fuminobu
authors.initials: F
authors.lastname: Tamalu
authors.affiliation: Department of Physiological Sciences, The Graduate University for Advanced Studies, Okazaki 444-8585, Japan, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki 444-8787, Japan, Division of Cell Signaling, National Institute for Physiological Sciences, and.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
authors.affiliation: From the Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Ishizaki
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D015870:Gene Expression; D018698:Glutamic Acid / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010704:Phorbols / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D050916:TRPV Cation Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism*
chemical_list: C517592:4alpha-phorbol 12,13-didecanone; D010704:Phorbols; D018094:Receptors, Metabotropic Glutamate; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; C104077:metabotropic glutamate receptor type 1; D016718:Arachidonic Acid; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D002118:Calcium
keywords: ATP; Astrocytes; Gliotransmitter; Glutamate; Synapses; TRP Channels; TRPV4
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