Pannexin

From discovery to bedside in 11±4 years?

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Pannexin1 (Panx1) originally was discovered as a gap junction related protein. However, rather than forming the cell-to-cell channels of gap junctions, Panx1 forms a mechanosensitive and highly ATP permeable channel in the cell membrane allowing the exchange of molecules between the cytoplasm and the extracellular space. The list of arguments for Panx1 representing the major ATP release channel includes: (1) Panx1 is expressed in (all?) cells releasing ATP in a non-vesicular fashion, such as erythrocytes; (2) in cells with polar release of ATP, Panx1 is expressed at the ATP release site, such as the apical membrane in airway epithelial cells; (3) the pharmacology of Panx1 channels matches that of ATP release; (4) mutation of Panx1 in strategic positions in the protein modifies ATP release; and (5) knockdown or knockout of Panx1 attenuates or abolishes ATP release. Panx1, in association with the purinergic receptor P2X7, is involved in the innate immune response and in apoptotic/pyroptotic cell death. Inflammatory processes are responsible for amplification of the primary lesion in CNS trauma and stroke. Panx1, as an early signal event and as a signal amplifier in these processes, is an obvious target for the prevention of secondary cell death due to inflammasome activity. Since Panx1 inhibitors such as probenecid are already clinically tested in different settings they should be considered for therapy in stroke and CNS trauma.

Original languageEnglish
Pages (from-to)150-159
Number of pages10
JournalBrain Research
Volume1487
DOIs
StatePublished - Dec 3 2012

Fingerprint

Adenosine Triphosphate
Stroke
Purinergic P2X7 Receptors
Inflammasomes
Polar Bodies
Probenecid
Connexins
Gap Junctions
Wounds and Injuries
Extracellular Space
Secondary Prevention
Innate Immunity
Cytoplasm
Cell Death
Erythrocytes
Epithelial Cells
Cell Membrane
Pharmacology
Mutation
Membranes

Keywords

  • Apoptosis
  • Gap junction
  • Glibenclamide
  • Inflammasome
  • Pannexin
  • Probenecid

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Pannexin : From discovery to bedside in 11±4 years? / Dahl, Gerhard; Keane, Robert.

In: Brain Research, Vol. 1487, 03.12.2012, p. 150-159.

Research output: Contribution to journalArticle

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