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摘要
During neuronal activity in the mammalian brain, the K1 released into the synaptic space is initially buffered by the astrocytic compartment. In parallel, the extracellular space (ECS) shrinks, presumably due to astrocytic cell swelling. With the Na+/K+/2Cl(-) cotransporter and the Kir4.1/AQP4 complex not required for the astrocytic cell swelling in the hippocampus, the molecular mechanisms underlying the activity-dependent ECS shrinkage have remained unresolved. To identify these molecular mechanisms, we employed ion-sensitive microelectrodes to measure changes in ECS, [K1](o) and [H-1](o)/pH(o) during electrical stimulation of rat hippocampal slices. Transporters and receptors responding directly to the K+ and glutamate released into the extracellular space (the K+/Cl- cotransporter, KCC, glutamate transporters and G protein-coupled receptors) did not modulate the extracellular space dynamics. The HCO3--transporting mechanism, which in astrocytes mainly constitutes the electrogenic Na+/HCO3- cotransporter 1 (NBCe1), is activated by the K+-mediated depolarization of the astrocytic membrane. Inhibition of this transporter reduced the ECS shrinkage by similar to 25% without affecting the K+ transients, pointing to NBCe1 as a key contributor to the stimulus-induced astrocytic cell swelling. Inhibition of the monocarboxylate cotransporters (MCT), like-wise, reduced the ECS shrinkage by similar to 25% without compromising the K1 transients. Isosmotic reduction of extracellular Cl2 revealed a requirement for this ion in parts of the ECS shrinkage. Taken together, the stimulusevoked astrocytic cell swelling does not appear to occur as a direct effect of the K+ clearance, as earlier proposed, but partly via the pH-regulating transport mechanisms activated by the K+-induced astrocytic depolarization and the activity-dependent metabolism.
- 出版日期2017-10
