Changes in the spontaneous calcium oscillations for the development of the preconditioning-induced ischemic tolerance in neuron/astrocyte co-culture.

Spontaneous Ca(2+) oscillations are believed to contribute to the regulation of gene expression. Here we investigated whether and how the dynamics of Ca(2+) oscillations changed after sublethal preconditioning (PC) for PC-induced ischemic tolerance in neuron/astrocyte co-cultures. The frequency of spontaneous Ca(2+) oscillations significantly decreased between 4 and 8 h after the end of PC in both neurons and astrocytes. Treatment with 2-APB, an inhibitor of IP3 receptors, decreased the oscillatory frequency, induced ischemic tolerance and a down-regulation of glutamate transporter GLT-1 contributing to the increase in the extracellular glutamate during ischemia. The expression of GLT-1 is known to be up-regulated by PACAP. Treatment with PACAP38 increased the oscillatory frequency, and antagonized both the PC-induced down-regulation of GLT-1 and ischemic tolerance. These results suggested that the PC suppressed the spontaneous Ca(2+) oscillations regulating the gene expressions of various proteins, especially of astrocytic GLT-1, for the development of the PC-induced ischemic tolerance.