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Connexins pp 287-301 | Cite as

Pannexins or Connexins?

  • Gerhard Dahl
  • Andrew L. Harris

Abstract

Pannexins are a family of three vertebrate proteins that have moderate sequence homology with the innexin proteins, which compose gap junction channels in protostomes, including most invertebrates. However, it appears that in contrast to innexins, pannexins do not have the ability to form gap junction channels. They do, however, form nonjunctional plasma membrane channels (pannexons) that mediate regulated flux of molecules in the size range of second messengers between cytoplasm and the extracellular space. The dye permeability and pharmacological sensitivities of pannexin channels overlap those of connexin hemichannels, so it is possible that many of the phenomena that have been attributed to connexin hemichannels are in fact mediated by pannexons. For this reason, identifying which protein is involved in a particular cellular physiology requires careful evaluation of the specific conditions and requirements in each case. Several lines of experimentation have led to the suggestion that the adenosine triphosphate (ATP) release channel, a crucial element in the initiation and propagation of intercellular Ca2+ waves, is a connexin hemichannel. However, based on recently revealed properties of pannexin channels, which include mechanosensitivity and activation by cytoplasmic Ca2+, the pannexon must be considered a prime candidate for the ATP release channel. Pannexons also appear to form the large ATP-permeable pore that is activated by the purinergic P2X7 receptor complex, which is involved in inflammation.

Keywords

Pannexin Innexin Connexin Gap junction Hemichannel Pannexon ATP release Calcium wave P2Y receptor P2X7 receptor Cx32 Cx38 Cx43 

Notes

Acknowledgments

The authors thank Drs. Nirupa Chaudhari, Silviu Locovei, Ken Muller, and William Silverman for helpful discussions and reading the manuscript. Work in the lab of G.D. on pannexin channels is supported by National Institutes of Health (NIH) grant GM48610.

Note added in proof: A reagent known to attenuate nucleotide release has been recently reported to inhibit pannexin but not connexin channels; Silverman W, Locovei S, Dahl GP. Proenecid, a gout remedy, inhibits pannexin 1 channels. Am J Physiol. 2008;295:C761-7.

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© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Physiology and BiophysicsUniversity of Miami School of MedicineMiamiUS

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