Cytosolic free calcium and ATP in synaptosomes after ischemia.

Elevations in cytosolic free calcium ([Ca2+]i) precede electrophysiological alterations due to ischemia in vivo. An in vitro model of these changes would help to elucidate their molecular basis. A model of postdecapitative ischemia was used to study these interactions. Nerve endings (i.e. synaptosomes) were isolated either immediately after decapitation or at various time periods after decapitation. Synaptosomal [Ca2+]i and ATP concentrations were determined during a basal period and following depolarization. K(+)-depolarization produced an initial spike of [Ca2+]i that was followed by a new equilibrium value. Ischemia elevated the basal [Ca2+]i and the new equilibrium [Ca2+]i after KCl but suppressed the [Ca2+]i spike. However, the difference between the basal [Ca2+]i and the new equilibrium [Ca2+]i after K(+)-depolarization did not vary with ischemia. Although ischemia reduced ATP, K(+)-depolarization did not alter ATP concentrations in either the controls or the ischemia group, which suggests that synaptosomal mitochondria can meet an energy demand after ischemia. ATP was inversely related to the basal or the new equilibrium [Ca2+]i following depolarization. These changes in [Ca2+]i may underlie the alterations in neurotransmitter release and cell death following ischemia. This appears to be a useful model in which to study the molecular basis of ischemia induced changes in [Ca2+]i.