Bradykinin-induced communication between astrocytes and neurons is mediated by glutamate released via volume-sensitive outwardly rectifying anion channels

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Application of bradykinin (BK) induced cytosolic Ca²⁺ rise in cultured mouse cortex astrocytes as well as neurons when co-cultured with astrocytes. However, BK failed to induce any Ca²⁺ response in the neurons cultured alone. In the co-culture system, a blocker of volume-sensitive outwardly rectifying (VSOR) anion channel, phloretin or DIDS, or that of NMDA receptor, AP-5, significantly suppressed BK-induced Ca²⁺ response in neurons but not in astrocytes. Also, astrocytes, but not neurons, were found to respond to BK with activation of whole-cell chloride currents. Although BK-stimulated astrocytes did not exhibit significant cell swelling, BK-activated anionic currents showed the properties phenotypic of VSOR anion channel; that is, moderate outward rectification, inhibition by osmotic shrinkage, sensitivity to phloretin and DIDS, dependence of intracellular ATP, and permeability to glutamate. BK stimulation was also found to induce release of glutamate, but not ATP, from astrocytes in a manner sensitive to phloretin, hypertonicity and blockers of BK receptors. These results suggest that glutamate released from astrocytes via their VSOR anion channels serves as a signal mediating the BK-induced glia-neuron interaction. [J Physiol Sci. 2007;57 Suppl:S126]