VRACs CARVe a Path for Novel Mechanisms of Communication in the CNS

Because the brain is encased by the skull, the ability to control cell volume in the brain is crucial, and pathological conditions that disturb cell volume homeostasis may severely compromise neural function and survival. Astrocytes are the main cell type to show swelling in response to pathological conditions. More recently, a role for swelling-induced neurotransmitter release from astrocytes under nonpathological conditions has been reported. Astrocytes express a volume-regulated anion channel (VRAC) that is involved in volume homeostasis. In addition to transporting chloride, VRACs allow the efflux of chloride and amino acids such as taurine, glutamate, and aspartate. Glutamate and aspartate are potent activators of neuronal glutamate receptors. Therefore, this nonsynaptic form of cellular communication may modulate neuronal excitability and synaptic activity.