Displacement of extracellular chloride by sulfated glycosaminoglycans of the brain’s extracellular matrix

Abstract

AbstractGABA is the primary inhibitory neurotransmitter. Membrane currents evoked by GABAAreceptor activation have uniquely small driving forces: their reversal potential (EGABA) is very close to the resting membrane potential. As a consequence, GABAAcurrents can flow in either direction, depending on both the membrane potential and the local intra and extracellular concentrations of the primary permeant ion, chloride (Cl). Cytoplasmic Cl concentrations vary widely due to displacement of mobile Cl ions by relatively immobile anions. Here we describe new reporters of extracellular chloride (Cl-o) and demonstrate that Cl is displaced in the extracellular space by high and spatially heterogenous concentrations of sulfated glycosaminoglycans. The mean Cl-ois only half the canonical concentration, i.e. the Cl concentration in the cerebrospinal fluid. Cl-omicrodomains provide a mechanism to link the highly stable distribution of GAGs in the brain’s extracellular space to neuronal signal processing via the effects on the amplitude and direction of GABAAtransmembrane Cl currents.