Description:
Astrocytes are an important source of extracellular ATP in the brain. Regulated release of ATP from astrocytes occurs in response to diverse metabolic, mechanical, or inflammatory stimuli. Non‐junctional hemichannels composed of connexin 43 have been shown to be a major conduit for release of ATP from murine astrocytes in response to hypoxia, but the role of non‐junctional connexin hemichannels in G‐protein coupled receptor (GPCR) mediated ATP release is not determined. Previously, using 1321N1 human astrocytes we found that rapid accumulation of active GTP‐bound Rho in response to GPCR activation greatly enhances Ca2+ dependent ATP release. GPCR induced ATP release from 1321N1 cells is attenuated by carbenoxolone, flufenamic acid, and probenecid. These structurally unrelated compounds are non‐selective inhibitors of non‐junctional hemichannels. Here we investigate the contribution of connexin 43 non‐junctional hemichannels to GPCR induced ATP release from 1321N1 astrocytes by connexin 43 overexpression and connexin 43 knockdown.