GABA Not Only a Neurotransmitter: Osmotic Regulation by GABA(A)R Signaling

Mature macroglia and almost all neural progenitor types express γ-aminobutyric (GABA) A receptors (GABA(A)Rs), whose activation by ambient or synaptic GABA, leads to influx or efflux of chloride (Cl(−)) depending on its electro-chemical gradient (E(Cl)). Since the flux of Cl(−) is indissolubly associated to that of osmotically obliged water, GABA(A)Rs regulate water movements by modulating ion gradients. In addition, since water movements also occur through specialized water channels and transporters, GABA(A)R signaling could affect the movement of water by regulating the function of the channels and transporters involved, thereby affecting not only the direction of the water fluxes but also their dynamics. We will here review recent observations indicating that in neural cells GABA(A)R-mediated osmotic regulation affects the cellular volume thereby activating multiple intracellular signaling mechanisms important for cell proliferation, maturation, and survival. In addition, we will discuss evidence that the osmotic regulation exerted by GABA may contribute to brain water homeostasis in physiological and in pathological conditions causing brain edema, in which the GABAergic transmission is often altered.