TRP Channels Coordinate Ion Signalling in Astroglia
Astroglial excitability is based on highly spatio-temporally coordinated fluctuations of intracellular ion concentrations, among which changes in Ca2+ and Na+ take the leading role. Intracellular signals mediated by Ca2+ and Na+ target numerous molecular cascades that control gene expression, energy production and numerous homeostatic functions of astrocytes. Initiation of Ca2+ and Na+ signals relies upon plasmalemmal and intracellular channels that allow fluxes of respective ions down their concentration gradients. Astrocytes express several types of TRP channels of which TRPA1 channels are linked to regulation of functional expression of GABA transporters, whereas TRPV4 channels are activated following osmotic challenges and are up-regulated in ischaemic conditions. Astrocytes also ubiquitously express several isoforms of TRPC channels of which heteromers assembled from TRPC1, 4 and/or 5 subunits that likely act as stretch-activated channels and are linked to store-operated Ca2+ entry. The TRPC channels mediate large Na+ fluxes that are associated with the endoplasmic reticulum Ca2+ signalling machinery and hence coordinate Na+ and Ca2+ signalling in astroglia.
KeywordsAstrocyte Ca2+ signalling Na+ signalling Metabotropic receptors, endoplasmic reticulum TRPC channels TRPCA1 TRPV4 Store-operated Ca2+ entry Stretch-activated channels Mechanosensitivity Volume regulation Plasticity Brain homeostasis
Authors’ research was supported by Alzheimer’s Research Trust (UK) Programme Grant (ART/PG2004A/1) to A.V. and by National Science Foundation (CBET 0943343) grant to V.P. R.C.R. was additionally funded by UCSF Neuroscience and Schizophrenia T32 (MH 089920).
Conflict of Interest
The authors declare that they have no conflict of interest.
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