TRPA1 channels regulate astrocyte resting calcium levels and inhibitory synapse efficacy via GAT-3

Shigetomi, Eiji; Tong, Xiaoping; Kwan, Kelvin Y.; Corey, David P.; Khakh, Baljit S.

doi:10.1038/nn.3000

ScienceOpen: research and publishing network

For Publishers

For Researchers

Blog
About

Search
Advanced search

views

recommends

Record: found
Abstract: found
Article: not found

TRPA1 channels regulate astrocyte resting calcium levels and inhibitory synapse efficacy via GAT-3

research-article

Author(s): Eiji Shigetomi ¹ , Xiaoping Tong ¹ , Kelvin Y. Kwan ³ , David P. Corey ³ , Baljit S. Khakh ¹ ^, ²

Publication date (Electronic): 11 December 2011

Journal: Nature Neuroscience

Read this article at

ScienceOpenPublisher PMC

Bookmark

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Astrocytes contribute to the formation and function of synapses and are found throughout the brain where they display intracellular store mediated Ca ²⁺ signals. Here, using a membrane tethered genetically encoded calcium indicator (Lck-GCaMP3), we report the serendipitous discovery of a novel Ca ²⁺ signal in rat hippocampal astrocyte-neuron co-cultures. We found that TRPA1 channel mediated Ca ²⁺ fluxes give rise to frequent and highly localised near membrane “spotty” Ca ²⁺ microdomains that contribute significantly to resting Ca ²⁺ levels of astrocytes. Mechanistic evaluations in brain slices show that decreasing astrocyte resting Ca ²⁺ levels mediated by TRPA1 channels decreased interneuron inhibitory synapse efficacy by reducing GABA transport via GAT-3, thus elevating extracellular GABA levels. Our data indicate how a novel transmembrane Ca ²⁺ source (TRPA1) targets a transporter (GAT-3) in astrocytes to regulate inhibitory synapses.

Related collections

Most cited references 40

Record: found
Abstract: found
Article: not found

Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin.

Michael Bandell, Gina M Story, Sun Wook Hwang … (2004)

Six members of the mammalian transient receptor potential (TRP) ion channels respond to varied temperature thresholds. The natural compounds capsaicin and menthol activate noxious heat-sensitive TRPV1 and cold-sensitive TRPM8, respectively. The burning and cooling perception of capsaicin and menthol demonstrate that these ion channels mediate thermosensation. We show that, in addition to noxious cold, pungent natural compounds present in cinnamon oil, wintergreen oil, clove oil, mustard oil, and ginger all activate TRPA1 (ANKTM1). Bradykinin, an inflammatory peptide acting through its G protein-coupled receptor, also activates TRPA1. We further show that phospholipase C is an important signaling component for TRPA1 activation. Cinnamaldehyde, the most specific TRPA1 activator, excites a subset of sensory neurons highly enriched in cold-sensitive neurons and elicits nociceptive behavior in mice. Collectively, these data demonstrate that TRPA1 activation elicits a painful sensation and provide a potential molecular model for why noxious cold can paradoxically be perceived as burning pain.

0 comments Cited 349 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Integrated brain circuits: astrocytic networks modulate neuronal activity and behavior.

Michael M. Halassa, Philip Haydon (2010)

The past decade has seen an explosion of research on roles of neuron-astrocyte interactions in the control of brain function. We highlight recent studies performed on the tripartite synapse, the structure consisting of pre- and postsynaptic elements of the synapse and an associated astrocytic process. Astrocytes respond to neuronal activity and neurotransmitters, through the activation of metabotropic receptors, and can release the gliotransmitters ATP, d-serine, and glutamate, which act on neurons. Astrocyte-derived ATP modulates synaptic transmission, either directly or through its metabolic product adenosine. d-serine modulates NMDA receptor function, whereas glia-derived glutamate can play important roles in relapse following withdrawal from drugs of abuse. Cell type-specific molecular genetics has allowed a new level of examination of the function of astrocytes in brain function and has revealed an important role of these glial cells that is mediated by adenosine accumulation in the control of sleep and in cognitive impairments that follow sleep deprivation.

0 comments Cited 224 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice.

Kishore V Kuchibhotla, Carli R Lattarulo, Bradley T. Hyman … (2009)

Although senile plaques focally disrupt neuronal health, the functional response of astrocytes to Alzheimer's disease pathology is unknown. Using multiphoton fluorescence lifetime imaging microscopy in vivo, we quantitatively imaged astrocytic calcium homeostasis in a mouse model of Alzheimer's disease. Resting calcium was globally elevated in the astrocytic network, but was independent of proximity to individual plaques. Time-lapse imaging revealed that calcium transients in astrocytes were more frequent, synchronously coordinated across long distances, and uncoupled from neuronal activity. Furthermore, rare intercellular calcium waves were observed, but only in mice with amyloid-beta plaques, originating near plaques and spreading radially at least 200 micrometers. Thus, although neurotoxicity is observed near amyloid-beta deposits, there exists a more general astrocyte-based network response to focal pathology.

0 comments Cited 220 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-journal-id): 9809671

Journal ID (pubmed-jr-id): 21092

Journal ID (nlm-ta): Nat Neurosci

Journal ID (iso-abbrev): Nat. Neurosci.

Title: Nature Neuroscience

ISSN (Print): 1097-6256

ISSN (Electronic): 1546-1726

Publication date Nihms-submitted: 20 December 2011

Publication date (Electronic): 11 December 2011

Publication date PMC-release: 01 July 2012

Volume: 15

Issue: 1

Pages: 70-80

Affiliations

[1 ]Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles USA CA 90095-1751

[2 ]Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles USA CA 90095-1751

[3 ]Howard Hughes Medical Institute, Harvard Medical School, Neurobiology, Goldenson 444, 220 Longwood Ave, Boston, MA 02115

Author notes

[Ψ ]Correspondence to BSK at Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, 53-263 CHS, Los Angeles, CA 90095-1751, Fax: 310 206 5661, Tel : 310 825 6258, bkhakh@ 123456mednet.ucla.edu

[*]

authors with equal contributions to experiments (ES and XT)

Article

Manuscript ID: nihpa337149

DOI: 10.1038/nn.3000

PMC ID: 3282183

PubMed ID: 22158513

SO-VID: 36585a06-bc44-4f1f-bf94-553435adfd3e

License:

Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms