Abstract
Spontaneous oscillations in the intracellular concentration of calcium (Ca2+ oscillations) contribute to the regulation of gene expression. Here we investigated whether and how the dynamics of Ca2+ oscillations changed after sublethal preconditioning (PC) for PC-induced ischemic tolerance in neuron/astrocyte co-cultures. Ischemia was simulated by depriving co-cultures of both oxygen and glucose (OGD). The frequency of spontaneous Ca2+ oscillations decreased significantly between 4 and 8 h after the end of PC in both neurons and astrocytes. The reduction in oscillatory frequency caused by treatment with 2-APB, an inhibitor of IP3 receptors, resulted in the development of ischemic tolerance, in a suppression of the rise in the extracellular concentration of glutamate during OGD, and in a down-regulation of the expression of the glutamate transporter GLT-1. The expression of GLT-1 is known to be up-regulated by treatment with PACAP. Treatment with PACAP6-38, an inhibitor of PACAP receptors, decreased the oscillatory frequency and GLT-1 protein levels, and induced ischemic tolerance. In contrast, treatment with PACAP38 increased the oscillatory frequency, and antagonized both the PC-induced down-regulation of GLT-1 expression and ischemic tolerance. These results suggested that the sublethal PC insult suppressed the spontaneous Ca2+ oscillations regulating various gene expressions for the development of the PC-induced ischemic tolerance. [J Physiol Sci. 2006;56 Suppl:S104]
