RT Journal Article
SR Electronic
T1 P2X<sub>7</sub> Receptors Mediate ATP Release and Amplification of Astrocytic Intercellular Ca<sup>2+</sup> Signaling
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1378
OP 1385
DO 10.1523/JNEUROSCI.3902-05.2006
VO 26
IS 5
A1 Sylvia O. Suadicani
A1 Celia F. Brosnan
A1 Eliana Scemes
YR 2006
UL http://www.jneurosci.org/content/26/5/1378.abstract
AB Modulation of synaptic transmission and brain microcirculation are new roles ascribed to astrocytes in CNS function. A mechanism by which astrocytes modify neuronal activity in the healthy brain depends on fluctuations of cytosolic Ca2+ levels, which regulate the release of “gliotransmitters” via an exocytic pathway. Under pathological conditions, however, the participation of other pathways, including connexin hemichannels and the pore-forming P2X7R, have been proposed but remain controversial. Through the use of genetically modified 1321N1 human astrocytoma cells and of spinal cord astrocytes derived from neonatal Cx43- and P2X7R-null mice, we provide strong evidence that P2X7Rs, but not Cx43 hemichannels, are sites of ATP release that promote the amplification of Ca2+ signal transmission within the astrocytic network after exposure to low divalent cation solution. Moreover, our results showing that gap junction channel blockers (heptanol, octanol, carbenoxolone, flufenamic acid, and mefloquine) are antagonists of the P2X7R indicate the inadequacy of using these compounds as evidence for the participation of connexin hemichannels as sites of gliotransmitter release.