HISTOCHEMICAL-STUDY OF CA2-ATPASE ACTIVITY IN ISCHEMIC CA1 PYRAMIDAL NEURONS IN THE GERBIL HIPPOCAMPUS()

Although cytosolic Ca2+ accumulation plays a pivotal role in delayed n euronal death. there have been no investigations on the role of the ce llular Ca2+ export system in this novel phenomenon. To clarify the fun ction of the Ca2+ pump in delayed neuronal death, the plasma membrane Ca2+-ATPase activity of CA1 pyramidal neurons was investigated ultracy tochemically in normal and ischemic gerbil hippocampus. To correlate e nzyme activity with delayed neuronal death, histochemical detection wa s performed at various recirculation times after 5 min of ischemia pro duced by occlusion of the bilateral carotid arteries. At 10 min after ischemia, CA1 pyramidal neurons showed weak Ca2+-ATPase activity. Alth ough enzyme activity had almost fully recovered 2 h after ischemia, it was reduced again 6 h after ischemia. Thereafter, Ca2+-ATPase activit y on the plasma membrane of CA1 pyramidal neurons decreased progressiv ely, losing its localization on day 3. On day 4 following ischemia, re action products were diffusely scattered throughout the whole cell bod y. Our results indicate that, after once having recovered from ischemi c damage, severe disturbance of the membrane Ca2+ export system procee ds from the early stage of delayed neuronal death and disturbs the re- export of accumulated cytosolic Ca2+, which might contribute to delaye d neuronal death. Occult disruption of Ca2+ homeostasis seems to occur from an extremely early stage of delayed neuronal death in CA1 pyrami dal cells.