Intracellular changes of K+, Na+, and Cl- were investigated by the aid of radiotracers in primary cultures of astrocytes when extracellular K+ was (1) increased from 3 to 12 mM and subsequently again decreased to 3 mM; and (2) increased from 5.4 to 54 mM with subsequent decrease to 5.4 mM. In both situations the K+ content increased by 50% within seconds, and it doubled within 1-2 min. The increase must be carrier mediated, because keeping the K X Cl product (Donnan equilibrium) constant did not lower the K+ accumulation rates. The Na+ content decreased when K+ was increased to 12 mM, but the decrease corresponded only to 10% of the accumulated K+. When K+ was increased to 54 mM, the Na+ content increased transiently. Cl- increased by about 15-25% of the accumulated K+. Return of extracellular K+ to original levels evoked a very fast K+ release, reversing all ion changes. The Na+ content increased transiently during the release process. For an interpretation of these observations, it is necessary to postulate endogenous production of an anion and of H+, which in turn is partly exchanged with Na+.
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