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The Journal of Neuroscience, April 15, 2000, 20(8):2835-2844

ATP-Mediated Glia Signaling

Maria Luisa Cotrina¹, Jane H.-C. Lin², Juan Carlos López-García³, Christian C. G. Naus⁴, and Maiken Nedergaard¹

Departments of ¹ Cell Biology and Anatomy and ² Pathology, New York Medical College, Valhalla, New York 10595, ³ Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, and ⁴ Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario N6A 5C1, Canada

Glia calcium signaling has recently been identified as a potent modulator of synaptic transmission. We show here that the spatial expansion of calcium waves is mediated by ATP and subsequent activation of purinergic receptors. Ectopic expression of gap junction proteins, connexins (Cxs), leads to an increase in both ATP release and the radius of calcium wave propagation. Cx expression was also associated with a phenotypic transformation, and cortical neurons extended longer neurites when co-cultured with Cx-expressing than with Cx-deficient cells. Purinergic receptor activation mediated both these effects, because treatment with receptor antagonists restored the glia phenotype and slowed neurite outgrowth. These results identify a key role of ATP in both short-term calcium signaling events and in long-term differentiation regulated by glia.

Key words: astrocytes; purinergic receptors; neuron; intracellular calcium; glioma; connexin

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Copyright © 2000 Society for Neuroscience  0270-6474/00/2082835-10$05.00/0

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