Inhibition of astrocyte gap junctional communication by ATP depletion is reversed by calcium sequestration.

We have studied the possible role of cellular energy status in the regulation of gap junction permeability in rat astrocytes in primary culture. Incubation with the mitochondrial respiratory chain inhibitor antimycin (5 ng/ml) for 16 h caused a significant decrease in ATP concentrations. This effect was accompanied by a dose-dependent inhibition of gap junction permeability as assessed by the scrape-loading/Lucifer yellow transfer technique. No cell death was observed following this treatment. Restoration of cellular ATP levels by a further 24 h incubation in antimycin-free medium reversed the inhibition of Lucifer yellow transfer caused by antimycin. The inhibition of Lucifer yellow transfer brought about by antimycin treatment was also reversed by a short incubation of the cells with the calcium chelator EGTA plus the calcium ionophore A23187. These results suggest that ATP depiction causes a reversible inhibition of gap junction permeability through a calcium-mediated mechanism.