Analysis of K+ accumulation reveals privileged extracellular region in the vicinity of glial cells in situ.

Astrocytes and oligodendrocytes in rat and mouse spinal cord slices, characterized by passive membrane currents during de- and hyperpolarizing stimulation pulses, express a high resting K+ conductance. In contrast to the case for astrocytes, a depolarizing prepulse in oligodendrocytes produces a significant shift of reversal potential (Vrev) to positive values, arising from the larger accumulation of K+ in the vicinity of the oligodendrocyte membrane. As a result, oligodendrocytes express large tail currents (Itail) after a depolarizing prepulse due to the shift of K+ into the cell. In the present study, we used a mathematical model to calculate the volume of the extracellular space (ECS) in the vicinity of astrocytes and oligodendrocytes (ESVv), defined as the volume available for K+ accumulation during membrane depolarization. A mathematical analysis of membrane currents revealed no differences between glial cells from mouse (n = 59) or rat (n = 60) spinal cord slices. We found that the Vrev of a cell after a depolarizing pulse increases with increasing Itail, expressed as the ratio of the integral inward current (Qin) after the depolarizing pulse to the total integral outward current (Qout) during the pulse. In astrocytes with small Itail and Vrev ranging from -50 to -70 mV, the Qin was only 3-19% of Qout, whereas, in oligodendrocytes with large Itail and Vrev between -20 and 0 mV, Qin/Qout was 30-75%. On the other hand, ESVv decreased with increasing values of Vrev. In astrocytes, ESVv ranged from 2 to 50 microm3, and, in oligodendrocytes, it ranged from 0.1 to 2.0 microm3. Cell swelling evoked by the application of hypotonic solution shifted Vrev to more positive values by 17.2 +/- 1.8 mV and was accompanied by a decrease in ESVv of 3.6 +/- 1.3 microm3. Our mathematical analysis reveals a 10-100 times smaller region of the extracellular space available for K+ accumulation during cell depolarization in the vicinity of oligodendrocytes than in the vicinity of astrocytes. The presence of such privileged regions around cells in the CNS may affect the accumulation and diffusion of other neuroactive substances and alter communication between cells in the CNS.