Ion homeostasis in rat brain in vivo: intra- and extracellular [Ca2+] and [H+] in the hippocampus during recovery from short-term, transient ischemia.
Changes in intra- and extracellular [Ca2+] and [H+], together with alterations in tissue PO2 and local blood flow, were measured in areas CA1 and CA3 of 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 PO2 above normal, with large fluctuations in both persisting for up to 4 h. In area CA1, [Ca2+]i decreased rapidly from an ischemic mean value of 30 microM to a control mean level of 73.1 nM in 20-30 min, whereas normalization of [Ca2+]e took approximately 1 h. Recovery of [Ca2+]i was accelerated by preischemic administration of a calcium antagonist, nifedipine, and a free radical scavenger, N-tert-butyl-alpha-phenylnitrone (PBN), but not by MK-801, a blocker of N-methyl-D-aspartate receptors. There was a secondary rise in [Ca2+]i in many cells beginning approximately 2 h after reperfusion. This was attenuated somewhat by PBN but not clearly influenced by either nifedipine or MK-801. Changes of [Ca2+]i in area CA3 were much smaller and slightly slower than in area CA1 and were not affected by the drugs mentioned above. In both areas CA1 and CA3, pHe and pHi fell 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 approximately 1 h, and in some microareas not at all. It is concluded that (a) effective mechanisms for restoring normal [Ca2+]i remain 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+]i and [Ca2+]e during 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.
Silver
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Department of Pathology and Microbiology, University of Bristol Medical School, England.
Erecińska
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D000818:Animals; D002118:Calcium / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D010100:Oxygen / Q000502:physiology; D011522:Protons; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D011522:Protons; D010100:Oxygen; D002118:Calcium