The signaling role for chloride in the bidirectional communication between neurons and astrocytes. (10th January 2019)

• Record Type: Journal Article
• Authors: Wilson, Corinne S.; Mongin, Alexander A.
• Is Part Of: Neuroscience letters. Volume 689(2019)
• Page Start: 33
• Page End: 44
• Publication Date: 2019-01-10
• Subjects: AE anion exchanger -- AVD apoptotic volume decrease -- EAAT excitatory amino acid transporter -- GABA γ-aminobutyric acid -- KCC K+-Cl− cotransporter -- NKCC Na+-K+-2Cl− cotransporter -- RVD regulatory volume decrease -- RVI regulatory volume increase -- VRAC volume-regulated anion channel; Neuron-astrocyte communication -- Chloride homeostasis -- Chloride channels -- KCC -- NKCC -- VRAC -- WNK; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2018.01.012
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: In this review, we make an argument that chloride (Cl − ) signaling is important in bidirectional neuron-astrocyte communication. Neurons modulate astrocytic [Cl − ]i through activation of neurotransmitter transporters, the cation-Cl − cotransporter NKCC1, and the volume-sensitive Cl − /anion channel VRAC. Astrocytes modify neuronal [Cl − ]i by releasing the inhibitory agonists, GABA and taurine, via VRAC and perhaps other permeability pathways. Recent studies discovered the [Cl − ]i -sensitivity of the WNK family protein kinases, making them putative [Cl − ]i sensors in neurons and astrocytes. Abstract: It is well known that the electrical signaling in neuronal networks is modulated by chloride (Cl − ) fluxes via the inhibitory GABAA and glycine receptors. Here, we discuss the putative contribution of Cl − fluxes and intracellular Cl − to other forms of information transfer in the CNS, namely the bidirectional communication between neurons and astrocytes. The manuscript (i) summarizes the generic functions of Cl − in cellular physiology, (ii) recaps molecular identities and properties of Cl − transporters and channels in neurons and astrocytes, and (iii) analyzes emerging studies implicating Cl − in the modulation of neuroglial communication. The existing literature suggests that neurons can alter astrocytic Cl − levels in a number of ways; via (a) the release of neurotransmitters and activation of glial transporters that have intrinsic Cl − conductance, (b) the metabotropic receptor-driven changes in activity of the electroneutral cation-Cl − cotransporter NKCC1, and (c) the transient, activity-dependent changes in glial cell volume which open the volume-regulated Cl − /anion channel VRAC. Reciprocally, astrocytes are thought to alter neuronal [Cl − ]i through either (a) VRAC-mediated release of the inhibitory gliotransmitters, GABA and taurine, which open neuronal GABAA and glycine receptor/Cl − channels, or (b) the gliotransmitter-driven stimulation of NKCC1. The most important recent developments in this area are the identification of the molecular composition and functional heterogeneity of brain VRAC channels, and the discovery of a new cytosolic [Cl − ] sensor − the Wnk family protein kinases. With new work in the field, our understanding of the role of Cl − in information processing within the CNS is expected to be significantly updated.