ATP-mediated glia signaling

Glia calcium signaling has recently been identified as a potent modulator o f 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. C x expression was also associated with a phenotypic transformation, and cort ical neurons extended longer neurites when co-cultured with Cx-expressing t han with Cx-deficient cells. Purinergic receptor activation mediated both t hese 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 differe ntiation regulated by glia.