EXTRACELLULAR K plus , PH, AND VOLUME CHANGES IN SPINAL-CORD OF ADULT-RATS AND DURING POSTNATAL-DEVELOPMENT

Activity-related transient changes in extracellular K+ concentration ([K+]e), extracellular pH (pH(e)), and extracellular volume (EC volume) were studied by means of ion-selective microelectrodes in the adult rat spinal cord in vivo and in neonatal rat spinal cords isolated from pups 3-14 days of age. Repetitive electrical nerve stimulation (10-100 Hz) in adults elicited increases in [K+]e by about 2.0-3.5 mM, followed by a poststimulation K+ undershoot and triphasic alkaline-acid-alkaline changes in pH(e). In 3- to 6-day-old pups, the [K+]e increased by as much as 6.5 mM at a stimulation frequency of 10 Hz, and this was accompanied by an alkaline shift. Increases in [K+]e as large as 1.3-2.5 mM accompanied by an alkaline shift were evoked by a single electrical stimulus. Stimulation in 10- to 13-day-old pups produced smaller [K+]e change and an acid shift, which was preceded by a small initial alkaline shift, as in adult rats. We conclude that glial cells buffer the activity-related [K+]e increase and alkaline pH, shifts. Mg2- blocked the alkaline but not the acid shift. Acetazolamide had no effect on the alkaline shift but blocked the acid shift. The alkaline shift was enhanced and the acid shift blocked by Ba2 + ,amiloride, 4-acetamido-4'-isothiocyanotostilbene-2,2'-disulfonic acid (SITS), and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Activity-related acid shifts therefore have a complex mechanism, which includes Na+/H+ exchange, Cl-/HCO3- exchange, or Na+/Cl-/H+/HCO3- antiport, Na+-HCO3- cotransport, and H+ efflux through voltage-sensitive H+ channels. Application of GABA evoked an alkaline shift in the pH(e) baseline, which was blocked by picrotoxin. The activation of GABA-gated Cl- channels, which induces a passive net efflux of bicarbonate, can therefore lead to an alkaline shift in pH(e). The poststimulation alkaline shifts were blocked by ouabain and reflect coupled clearance of K+ and H+ by active transport processes. The EC volume in the adult rat occupies about 20-25% of the tissue; in neonatal cord, 28-40%. Electrical or adequate stimulation-evoked ionic changes in adult rats were accompanied by shrinkage of the extracellular space by 20-50%. We conclude that the size of the EC volume is altered during stimulation of an afferent input, central nervous system development, and peripheral or central injury.