A permeant regulating its permeation pore: Inhibition of pannexin 1 channels by ATP

Feng Qiu, Gerhard Dahl

Research output: Contribution to journalArticle

159 Scopus citations

Abstract

Pannexin 1 forms a large membrane channel that, based on its biophysical properties and its expression pattern, is a prime candidate to represent an ATP release channel. Pannexin 1 channel activity is potentially deleterious for cells as indicated by its involvement in the P2X7 death complex. Here we describe a negative feedback loop controlling pannexin 1 channel activity. ATP, permeant to pannexin 1 channels, was found to inhibit its permeation pathway when applied extracellularly to oocytes expressing pannexin 1 exogenously. ATP analogues, including benzoylbenzoyl-ATP, suramin, and brilliant blue G were even more effective inhibitors of pannexin 1 currents than ATP. These compounds also attenuated the uptake of dyes by erythrocytes, which express pannexin 1. The rank order of the compounds in attenuation of pannexin 1 currents was similar to their binding affinities to the P2X7 receptor, except that receptor agonists and antagonists both were inhibitory to the channel. Mutational analysis identified R75 in pannexin 1 to be critical for ATP inhibition of pannexin 1 currents.

Original languageEnglish (US)
Pages (from-to)C250-C255
JournalAmerican Journal of Physiology - Cell Physiology
Volume296
Issue number2
DOIs
StatePublished - Feb 2009

Keywords

  • ATP release
  • Benzylbenzoyl-ATP
  • Brilliant blue G
  • erythrocyte
  • P2X7 receptor

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

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