ATP and potassium ions: A deadly combination for astrocytes

David G. Jackson, Junjie Wang, Robert Keane, Eliana Scemes, Gerhard Dahl

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 P2X 7R. 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.

Original languageEnglish
Article number4576
JournalScientific Reports
Volume4
DOIs
StatePublished - Apr 3 2014

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Astrocytes
Potassium
Adenosine Triphosphate
Ions
Caspase 3
Purinergic P2X7 Receptors
Extracellular Space
Cell Death
Binding Sites
Apoptosis

ASJC Scopus subject areas

  • General

Cite this

ATP and potassium ions : A deadly combination for astrocytes. / Jackson, David G.; Wang, Junjie; Keane, Robert; Scemes, Eliana; Dahl, Gerhard.

In: Scientific Reports, Vol. 4, 4576, 03.04.2014.

Research output: Contribution to journalArticle

Jackson, David G. ; Wang, Junjie ; Keane, Robert ; Scemes, Eliana ; Dahl, Gerhard. / ATP and potassium ions : A deadly combination for astrocytes. In: Scientific Reports. 2014 ; Vol. 4.
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