Ion Homeostasis in Rat Brain in vivo: Intra- and Extracellular [Ca2+] and [H+] in the Hippocampus during Recovery from Short-Term, Transient Ischemia

Abstract

Changes in intra- and extracellular [Ca2+] and [H+], together with alterations in tissue Po2and local blood flow, were measured in areas CA1and CA3of the hippocampus during recovery (up to 8 h) after an 8-min period of low-flow ischemia. Restoration of blood supply was followed by an immediate rise in flow and tissue Po2above normal, with large fluctuations in both persisting for up to 4 h. In area CA1, [Ca2+]idecreased rapidly from an ischemic mean value of 30 μ M to a control mean level of 73.1 n M in 20–30 min, whereas normalization of [Ca2+]etook ∼1 h. Recovery of [Ca2+]iwas accelerated by preischemic administration of a calcium antagonist, nifedipine, and a free radical scavenger, N-tert-butyl-α-phenylnitrone (PBN), but not by MK-801, a blocker of N-methyl-d-aspartate receptors. There was a secondary rise in [Ca2+]iin many cells beginning ∼2 h after reperfusion. This was attenuated somewhat by PBN but not clearly influenced by either nifedipine or MK-801. Changes of [Ca2+]iin area CA3were much smaller and slightly slower than in area CA1and were not affected by the drugs mentioned above. In both areas CA1and CA3, pHeand pHifell during ischemia to an average value of 6.2, from which there was a rapid initial recovery in the first 5–10 min when blood flow was restored. Thereafter tissue pH rose slowly and did not reach control levels for ∼1 h, and in some microareas not at all. It is concluded that (a) effective mechanisms for restoring normal [Ca2+]iremain intact after 8 min of low-flow ischemia; (b) in neurons of area CA1, some insidious change in the homeostasis of calcium triggers a secondary rise in its free cytosolic concentration, which may be causally related to activation of irreversible cell damage; and (c) the changes in [Ca2+]iand [Ca2+]eduring and following 8 min of ischemia can be adequately accounted for by movements of a fixed pool of Ca between intra- and extracellular compartments, and possible mechanisms are discussed.