Intrasynaptosomal Free Calcium Concentration During Rat Brain Development: Effects of Hypoxia, Aglycaemia, and Ischaemia

Abstract: The effects of hypoxia, aglycaemia, and hypoxia-aglycaemia on intrasynaptosomal free Ca²⁺ concentration (Ca²⁺]_i) have been investigated in rat brain synaptosomes prepared from animals aged 5, 10, 15, 20, 25, and 60 days. After 60 min of hypoxia there was no significant difference, when compared with controls, in basal Ca²⁺]_i or Ca²⁺]_i following depolarisation in all of the ages studied. Following 60 min of aglycaemia there was no significant difference from controls in Ca²⁺]_i of synaptosomes prepared from pups of ≤20 days, although a significant rise in Ca²⁺]_i was seen in preparations from animals >20 days old. Sixty minutes of hypoxia-aglycaemia led to a significant rise in Ca²⁺]_i only in preparations from animals 15–60 days old. With both aglycaemia and hypoxia-aglycaemia a progressive increase in the magnitude of the rise in Ca²⁺]_i was seen with development. These data suggest increases in Ca²⁺]_i in adult nerve terminals following prolonged aglycaemia and hypoxia-aglycaemia but no change following prolonged hypoxia. In contrast, no significant changes in Ca²⁺]_i values were apparent in neonatal nerve terminals under any of these conditions. In control synaptosomes with glucose and oxygen freely available, a decrease in resting and depolarised Ca²⁺]_i during development was seen, suggesting a change in calcium homeostasis within the nerve terminal as the brain develops. It is suggested that the mechanism underlying the relative resistance to ischaemic damage of neonatal brain as compared with adult brain may be related to the regulation of calcium at the nerve ending.