Calcium Movement in Ischemia-Tolerant Hippocampal CA1 Neurons after Transient Forebrain Ischemia in Gerbils

Abstract

Hippocampal CA1 neurons exposed to a nonlethal period (2 min) of ischemia, acquired tolerance to a subsequent lethal 5-min period of ischemia, which usually causes delayed-type neuronal death. Intracelluar Ca²⁺movements before and after the 5 min of forebrain ischemia were evaluated in gerbil hippocampal CA1 pyramidal neurons, had acquired tolerance in comparison with nonischemia-tolerant CA1 neurons. Evaluation was performed by observing the ultrastructural intracellular Ca²⁺distribution and the Ca²⁺adenosine triphosphatase (Ca²⁺-ATPase) activity using electron microscopic cytochemistry. In comparison with nonischemia-tolerant CA1 neurons, mitochondria of ischemia-tolerant CA1 neurons sequestered more Ca²⁺from the cytosomal fraction 15 min after the 5-min period of ischemia, and Ca²⁺deposits in these mitochondria were rapidly decreased. Plasma membrane Ca²⁺-ATPase activities were already significantly elevated before the 5 min of ischemia, and remained at a higher level subsequently compared to nonischemia-tolerant CA1 neurons. Changes in the mitochondrial Ca²⁺distribution and Ca²⁺-ATPase activities in ischemia-tolerant CA1 neurons after the 5-min period of ischemia showed a strong resemblance to those in CA3 neurons, which originally possess resistance to such periods of ischemia. These findings suggest that enhanced or maintained activities of mitochondrial Ca²⁺sequestration and plasma membrane Ca²⁺-ATPase reduced Ca²⁺toxicity following 5-min ischemia in terms of time, resulting in escape from delayed neuronal death.