Hypercapnia Modulates the Activity of Adenosine A1 Receptors and mitoKATP+-Channels in Rat Brain When Exposed to Intermittent Hypoxia

The mechanisms and signaling pathways of the neuroprotective effects of hypercapnia and its combination with hypoxia are not studied sufficiently. The study aims to test the hypothesis of the potentiating effect of hypercapnia on the systems of adaptation to hypoxia, directly associated with A1-adenosine receptors and mitochondrial ATP-dependent K+-channels (mitoK(ATP)(+)-channels). We evaluated the relative number of A1-adenosine receptors and mitoK(ATP)(+)-channels in astrocytes obtained from male Wistar rats exposed to various respiratory conditions (15 times of hypoxia and/or hypercapnia). In addition, the relative number of these molecules in astrocytes was evaluated on an in vitro model of chemical hypoxia, as well as in the cerebral cortex after photothrombotic damage. This study indicates an increase in the relative number of A1-adenosine receptors in astrocytes and in cells next to the stroke region of the cerebral cortex in rats exposed to hypoxia and hypercapnic hypoxia, but not hypercapnia alone. Hypercapnia and hypoxia increase the relative number of mitoK(ATP)(+)-channels in astrocytes and in cells of the peri-infarct region of the cerebral cortex in rats. In an in vitro study, hypercapnia mitigates the effects of acute chemical hypoxia observed in astrocytes for A1-adenosine receptors and mitoK(ATP)(+)-channels. Hypercapnia, unlike hypoxia, does not affect the relative number of A1 receptors to adenosine. At the same time, both hypercapnia and hypoxia increase the relative number of mitoK(ATP)(+)-channels, which can potentiate their protective effects with combined exposure. [GRAPHICS] .

Automated summary

The study found that the combination of hypercapnia and hypoxia can increase the relative number of A1-adenosine receptors and mitoK(ATP)(+)-channels in astrocytes, potentially enhancing their neuroprotective effects. However, hypercapnia alone does not have this effect.