Abstract
Although cytosolic Ca2+ accumulation plays a pivotal role in delayed neuronal death, there have been no investigations on the role of the cellular Ca2+ export system in this novel phenomenon. To clarify the function of the Ca2+-pump in delayed neuronal death, the plasma membrane Ca2+-ATPase activity of CA1 pyramidal neurons was investigated ultracytochemically in normal and ischemic gerbil hippocampus. To correlate enzyme activity with delayed neuronal death, histochemical detection was performed at various recirculation times after 5 min of ischemia produced by occlusion of the bilateral carotid arteries. At 10 min after ischemia, CA1 pyramidal neurons showed weak Ca2+-ATPase activity. Although enzyme activity had almost fully recovered 2 h after ischemia, it was reduced again 6 h after ischemia. Thereafter, Ca2+-ATPase activity on the plasma membrance of CA1 pyramidal neurons decreased progressively, losing its localization on day 3. On day 4 following ischemia, reaction products were diffusely scattered throughout the whole cell body. Our results indicate that, after once having recovered from ischemic damage, severe disturbance of the membrane Ca2+ export system proceeds from the early stage of delayed neuronal death and disturbs the re-export of accumulated cytosolic Ca2+, which might contribute to delayed neuronal death. Occult disruption of Ca2+ homeostasis seems to occur from an extremely early stage of delayed neuronal death in CA1 pyramidal cells.
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Akisaka T, Gay C (1985) Ultrastructural localization of calcium-activated adenosine triphosphatase (Ca2+-ATPase) in growth-plate cartilage. J Histochem Cytochem 33:925–932
Andiné P, Jacobson I, Hagberg H (1988) Calcium uptake evoked by electrical stimulation is enhanced post-ischemically and precedes delayed neuronal death in CA1 of rat hippocampus: involvement of N-methyl-D-aspartate receptors. J Cereb Blood Flow Metab 8:799–807
Ando T, Fujimoto K, Mayahara H, Miyajima H, Ogawa K (1981) A new one-step method for the histochemistry and cytochemistry of Ca2+-ATPase activity. Acta Histochem Cytochem 14:705–726
Bambauer HJ, Ueno S, Umar H (1984) Ultracytochemical localization of Ca2+-ATPase activity in pituicytes of neurohypophysis of the guinea pig. Cell Tissue Res 237:491–497
Baudry M, Lynch G (1980) Regulation of hippocampal glutamate receptors: evidence for the involvement of a calcium-activated protease. Proc Natl Acad Sci USA 77:2298–2302
Baudry M, Bundman MC, Smith EK, Lynch GS (1981) Micromolar calcium stimulates proteolysis and glutamate binding in rat brain synaptic membranes. Science 212:937–938
Benveniste H, Drejer J, Schousboe A, Diemer NH (1984) Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialisis. J Neurochem 43:1369–1374
Berridge MJ (1979) Modulation of nervous activity by cyclic nucleotides and calcium. In: Schmitt FO, Worden FG (eds) The neurosciences: fourth study program. MIT Press, Cambridge, pp 873–889
Berridge MJ, Irvine RF (1984) Inositol triphosphate, a novel second messenger in cellular signal transduction. Nature 312: 315–321
Choi DW (1988) Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage. Trends Neurosci 11:465–469
Deshpande JK, Siesjö BK, Wieloch T (1987) Calcium accumulation and neuronal damage in the rat hippocampus following cerebral ischemia. J Cereb Blood Flow Metab 7:89–95
Dienel GA (1984) Regional accumulation of calcium in postischemic rat brain. J Neurochem 43:913–925
Dux E, Mies G, Hossman KA, Siklos L (1987) Calcium in the mitochondria following brief ischemia of gerbil brain. Neurosci Lett 78:295–300
Ehrlich BE, Watras J (1988) Inositol 1,4,5-triphosphate activates a channel from smooth muscle sarcoplasmic reticulum. Nature 336:583–586
Endo M (1977) Calcium release from the sarcoplasmic reticulum. Physiol Rev 57:71–108
Fujimoto K, Ogawa K (1982) Enzyme cytochemical study of rat cardiac muscle. II. Ca2+-ATPase and ouabain sensitive, K-dependent p-nitrophenylphosphatase. Acta Histochem Cytochem 15:338–354
Hagberg H, Lehmann A, Sandberg M, Nystrom B, Jacobson I, Hamberger A (1985) Ischemia induced shift of inhibitory and excitatory amino acids from intra-to extracellular compartment. J Cereb Blood Flow Metab 5:413–419
Hansen AJ (1985) Effect of anoxia on ion distribution in the brain. Physiol Rev 65:101–148
Hara H, Sakamoto T, Kogure K (1993) Mechanism and pathogenesis of ischemia-induced neuronal damage. Prog Neurobiol 40:645–670
Kirino T (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239:57–69
Kirino T, Sano K (1984) Selective vulnerability in the gerbil hippocampus following transient ischemia. Acta Neuropathol (Berl) 62:201–208
Kirino T, Robinson HPC, Miwa A, Tamura A, Kawai N (1992) Disturbance of membrane function preceding ischemic delayed neuronal death in the gerbil hippocampus. J Cereb Blood Flow Metab 12:408–417
Martins E, Inamura K, Themner K, Malmqvist KG, Siesjö BK (1988) Accumulation of calcium and loss of potassium in the hippocampus following transient cerebral ischemia: a proton microprobe study. J Cereb Blood Flow Metab 8:531–538
Nicholson C, ten Bruggencate GT, Steinberg R, Stockle H (1977) Calcium modulation in brain extracellular microenvironment demonstrated with ion-selective micropipette. Proc Natl Acad Sci USA 74:1287–1290
Penniston JT (1982) The function and regulation of the calcium pump in the erythrocyte membrane. Ann NY Acad Sci 402: 296–303
Pulsinelli WA, Brierley JB, Plum F (1982) Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol 11:491–498
Rega AF (1986) The Ca2+ homeostasis. In: Rega AF, Garrahan PJ (eds) The Ca2+ pump of plasma membrane. CRC Press, Boca Raton, pp 13–20
Rothman SM, Olney JW (1986) Glutamate and the pathophysiology of hypoxic-ischemic brain damage. Ann Neurol 19: 105–111
Sakamoto N, Kogure K, Kato H, Ohtomo H (1986) Disturbed Ca2+ homeostasis in the gerbil hippocampus following brief transient ischemia. Brain Res 364:372–376
Siesjö BK, Bengtsson F (1989) Calcium fluxes, calcium antagonists, and calcium-related pathology in brain ischemia, hypoglycemia, and spreading depression: a unifying hypothesis. J Cereb Blood Flow Metab 9:127–140
Siesjö BK, Wieloch T (1985) Cerebral metabolism in ischemia: neurochemical basis for therapy. Br J Anaesth 57:47–62
Sims NR, Pulsinelli WA (1987) Altered mitochondrial respiration in selectively vulnerable brain subregions following transient forebrain ischemia in the rat. J Neurochem 49:1367–1374
Smith JS, Coronado R, Meissner G (1986) Single channel measurements of the calcium release from skeletal muscle sarcoplasmic reticulum. J Gen Physiol 88:573–588
Smith ML, Auer RN, Siesjö BK, (1986) The density and distribution of ischemic brain injury in the rat following 2–10 min of forebrain ischemia. Acta Neuropathol (Berl) 64:319–332
Streb H, Irvine RF, Berridge MJ, Schulz I (1983) Release of Ca2+ from a non-mitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-triphosphate. Nature 306:67–68
Strosznajder J (1980) Role of phospholipids in calcium accumulation in brain mitochondria from adult rat after ischemic anoxia and hypoxic hypoxia. Bull Acad Pol Sci Ser Sci Biol 27: 683–692
Tsubokawa H, Oguro K, Robinson HPC, Masuzawa T, Kirino T, Kawai N (1992) Abnormal Ca2+ homeostasis before cell death revealed by whole cell recording of ischemic CA1 hippocampal neurons. Neuroscience 49:807–817
Tsubokawa H, Oguro K, Robinson HPC, Masuzawa T, Rhee TSG, Takenawa T, Kawai N (1994) Inositol 1,3,4,5-tetrakishosphate as a mediator of neuronal death in ischemic hippocampus. Neuroscience 59:291–297
Tsubokawa H, Oguro K, Masuzawa T, Kawai N (1994) Ca2+-dependent non-NMDA receptor-mediated synaptic currents in ischemic CA1 hippocampal neurons. J Neurophysiol 71:1190–1196
Ueno S, Bambauer HJ, Umar H, Ueck M, Ogawa K (1984) Ultracytochemical study of Ca2+-ATPase and K+-NPPase activities on retinal photoreceptors of the guinea pig. Cell Tissue Res 237:479–489
Wachstein M, Meisel E (1957) Histochemistry of hepatic phosphatases at a physiological pH with special reference to the demonstration of bile canaliculi. Am J Clin Pathol 27:13–23
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Oguro, K., Nakamura, M. & Masuzawa, T. Histochemical study of Ca2+-ATPase activity in ischemic CA1 pyramidal neurons in the gerbil hippocampus. Acta Neuropathol 90, 448–453 (1995). https://doi.org/10.1007/BF00294804
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DOI: https://doi.org/10.1007/BF00294804