Format

Send to

Choose Destination
Sci Rep. 2014 Apr 3;4:4576. doi: 10.1038/srep04576.

ATP and potassium ions: a deadly combination for astrocytes.

Author information

1
Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, Florida 33136.
2
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, 10461.

Abstract

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.

PMID:
24694658
PMCID:
PMC3974143
DOI:
10.1038/srep04576
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center