Extracellular ionic variations during spreading depression

Changes in the concentrations of K+, Ca2+, Na+ and Cl− were measured during spreading depression in the exposed lissencephalic cerebellar molecular layer of the catfish,Corydoras aneus. Liquid ion exchanger ion-selective microelectrodes were used in pairs to monitor simultaneously changes in the concentrations of two ionic species in the extracellular space. Normothermic spreading depression in the catfish cerebellum consists of a slow negative potential shift that develops at a rate of 2–3mV/s, reaches an amplitude of −25 mV, lasts 1–6 min and propagates at a rate of 0.5–1.5 mm/min. [K+]o rises from a resting level of 2.3–35 mM at the peak of spreading depression. Between 20 and 40s later [Ca2+]o falls from 2.2 mM to 0.8 mM and [Na+]o and [Cl−]o decrease from 149 to 57 mM and 137 to 47 mM respectively at approximately the same time. [Ca2+]o, [Na+]o and [Cl−]o decreases begin when [K+]o exceeds 10 mM. These results establish the magnitude and temporal sequence of the major ion concentration changes in extracellular space during spreading depression. The earliest extracellular precursor of spreading depression is a rise in [K+]o. In light of the equality of [Na+]o and [Cl−]o changes and the rise in [K+]o, electroneutrality in extracellular space involved may be maintained by the net accumulation of some unidentified anion equivalent to the rise in [K+]o. Alternatively, no net accumulation is needed if some extracellular anions are impermeant and the volume of extracellular space decreases. The sum of the extracellular ion concentrations suggests that the ionic strength of extracellular space decreases by greater than one-third during spreading depression. These results demonstrate that the brain is capable of establishing and recovering from local ionic inhomogenejties.