High synaptic activity is associated with a transient decrease in the extracellular space surrounding the active synapses. This is physiologically important, as local restriction of the extracellular space modulates the efficacy of synaptic transmission by (1) increasing the local concentration of neurotransmitter, and (2) limiting the spillover of the transmitter from the synaptic cleft. This local shrinkage of the extracellular space following neuronal activity is regulated by water transport across astroglial membranes and water redistribution through the glial syncytium. Water accumulated at the site of high neuronal activity is released distantly, which causes an increase in extracellular volume. Such coordinated changes in extracellular volume have been directly observed, for example, in the cortex, where stimulation of neuronal afferents caused a local decrease in extracellular volume in layer IV and a simultaneous increase in the extracellular space in layer I. These changes in extracellular volume are directly coupled to the astroglial syncytium, as they can be eliminated following uncoupling of the glial cells by pharmacological inhibition of gap junctions.
This redistribution of water during neuronal activity is mediated through the aquaporins, which show a very special distribution across the astrocyte plasmalemma. Aquaporin channels (especially AQP4) are clustered in the perivascular and subpial endfeet and in perisynaptic processes and are colocalized with the Kir4.1 channel subtype (Figure 7.11). Synaptic activity causes local elevations of extracellular concentrations of glutamate, K+ and CO2; glutamate and K+ are accumulated by astrocytes through glutamate transporter and Kir channels, respectively, whereas CO2 is transported into the astrocyte via Na+/HCO- cotransporter. These events increase local osmotic pressure at the astrocyte membrane, which favours water intake through the aquaporins; removal of extracellular water leads to shrinkage of the extracellular space. Locally accumulated water is redistributed through the astroglial network and is extruded distantly (also through aquaporins) therefore increasing the extracellular volume near the place of efflux.
This scheme of water redistribution following neuronal activity is equivalent to that of spatial K+ buffering (Chapter 7.7.1), which suggested possible coordination between water and K+ transport across astroglial membranes. This idea gained credibility recently, after direct coupling between aquaporins and Kir channels (Kjj.4.1) was discovered on a molecular level. Furthermore it appears that transgenic mice lacking aquaporins in the perivascular astrocytic processes also have an impaired spatial K+ buffering.
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