| First Author | Jackson DG | Year | 2014 |
| Journal | Sci Rep | Volume | 4 |
| Pages | 4576 | PubMed ID | 24694658 |
| Mgi Jnum | J:265035 | Mgi Id | MGI:6198795 |
| Doi | 10.1038/srep04576 | Citation | Jackson DG, et al. (2014) ATP and potassium ions: a deadly combination for astrocytes. Sci Rep 4:4576 |
| abstractText | The ATP release channel Pannexin1 (Panx1) is self-regulated, i.e. the permeant ATP inhibits the channel from the extracellular space. The affinity of the ATP binding site is lower than that of the purinergic P2X7 receptor allowing a transient activation of Panx1 by ATP through P2X7R. Here we show that the inhibition of Panx1 by ATP is abrogated by increased extracellular potassium ion concentration ([K(+)]o) in a dose-dependent manner. Since increased [K(+)]o is also a stimulus for Panx1 channels, it can be expected that a combination of ATP and increased [K(+)]o would be deadly for cells. Indeed, astrocytes did not survive exposure to these combined stimuli. The death mechanism, although involving P2X7R, does not appear to strictly follow a pyroptotic pathway. Instead, caspase-3 was activated, a process inhibited by Panx1 inhibitors. These data suggest that Panx1 plays an early role in the cell death signaling pathway involving ATP and K(+) ions. Additionally, Panx1 may play a second role once cells are committed to apoptosis, since Panx1 is also a substrate of caspase-3. |
