ATP signaling is deficient in cultured pannexin1-null mouse astrocytes

Sylvia O. Suadicani, Rodolfo Iglesias, Junjie Wang, Gerhard Dahl, David C. Spray, Eliana Scemes

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Pannexins (Panx1, 2, and 3) comprise a group of proteins expressed in vertebrates that share weak yet significant sequence homology with the invertebrate gap junction proteins, the innexins. In contrast to the other vertebrate gap junction protein family (connexin), pannexins do not form intercellular channels, but at least Panx1 forms nonjunctional plasma membrane channels. Panx1 is ubiquitously expressed and has been shown to form large conductance (500 pS) channels that are voltage dependent, mechanosensitive, and permeable to relatively large molecules such as ATP. Pharmacological and knockdown approaches have indicated that Panx1 is the molecular substrate for the so-called "hemichannel" originally attributed to connexin43 and that Panx1 is the pore-forming unit of the P2X7 receptor. Here, we describe, for the first time, conductance and permeability properties of Panx1-null astrocytes. The electrophysiological and fluorescence imaging analyses performed on these cells fully support our previous pharmacological and Panx1 knockdown studies that showed profoundly lower dye uptake and ATP release than wild-type untreated astrocytes. As a consequence of decreased ATP paracrine signaling, intercellular calcium wave spread is altered in Panx1-null astrocytes. Moreover, we found that in astrocytes as in Panx1-expressing oocytes, elevated extracellular K+ activates Panx1 channels independently ofmembrane potential. Thus, on the basis of our present findings and our previous report, we propose that Panx1 channels serve as K+ sensors for changes in the extracellular milieu such as those occurring under pathological conditions.

Original languageEnglish (US)
Pages (from-to)1106-1116
Number of pages11
JournalGLIA
Volume60
Issue number7
DOIs
StatePublished - Jul 2012

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Astrocytes
Connexins
Adenosine Triphosphate
Vertebrates
Paracrine Communication
Purinergic P2X7 Receptors
Pharmacology
Connexin 43
Calcium Signaling
Optical Imaging
Invertebrates
Sequence Homology
Ion Channels
Oocytes
Permeability
Coloring Agents
Cell Membrane
Proteins

Keywords

  • Calcium waves
  • Connexin
  • Gap junction
  • Glia
  • P2X receptor
  • Pannexin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

ATP signaling is deficient in cultured pannexin1-null mouse astrocytes. / Suadicani, Sylvia O.; Iglesias, Rodolfo; Wang, Junjie; Dahl, Gerhard; Spray, David C.; Scemes, Eliana.

In: GLIA, Vol. 60, No. 7, 07.2012, p. 1106-1116.

Research output: Contribution to journalArticle

Suadicani, Sylvia O. ; Iglesias, Rodolfo ; Wang, Junjie ; Dahl, Gerhard ; Spray, David C. ; Scemes, Eliana. / ATP signaling is deficient in cultured pannexin1-null mouse astrocytes. In: GLIA. 2012 ; Vol. 60, No. 7. pp. 1106-1116.
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