A novel subtype of astrocytes expressing TRPV4 regulates neuronal excitability via release of gliotransmitters [Cell Biology]

April 15th, 2014 by Shibasaki, K., Ikenaka, K., Tamalu, F., Tominaga, M., Ishizaki, Y.

Astrocytes play active roles in the regulation of synaptic transmission. Neuronal excitation can evoke Ca2+ transients in astrocytes, and these Ca2+ transients can modulate neuronal excitability. While 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. Following activation, both TRPV4+ and TRPV4- astrocytes release glutamate, which acts as an excitatory gliotransmitter to increase synaptic transmission through type 1 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.