Extracellular zinc and ATP-gated P2X receptor calcium entry channels: New zinc receptors as physiological sensors and therapeutic targets

Erik M. Schwiebert, Lihua Liang, Nai Lin Cheng, Clintoria Richards Williams, Dragos Olteanu, Elisabeth A. Welty, Akos Zsembery

Research output: Contribution to journalReview article

13 Citations (Scopus)

Abstract

In this review, we focus on two attributes of P2X receptor channel function, one essential and one novel. First, we propose that P2X receptors are extracellular sensors as well as receptors and ion channels. In particular, the large extracellular domain (that comprises 70% of the molecular mass of the receptor channel protein) lends itself to be a cellular sensor. Moreover, its exquisite sensitivity to extracellular pH, ionic strength, and multiple ligands evokes the function of a sensor. Second, we propose that P2X receptors are extracellular zinc receptors as well as receptors for nucleotides. We provide novel data in multiple publications and illustrative data in this invited review to suggest that zinc triggers ATP-independent activation of P2X receptor channel function. In this light, P2X receptors are the cellular site of integration between autocrine and paracrine zinc signaling and autocrine and paracrine purinergic signaling. P2X receptors may sense changes in these ligands as well as in extracellular pH and ionic strength and transduce these sensations via calcium and/or sodium entry and changes in membrane potential.

Original languageEnglish
Pages (from-to)299-310
Number of pages12
JournalPurinergic Signalling
Volume1
Issue number4
DOIs
Publication statusPublished - Dec 1 2005

Keywords

  • Calcium
  • Cystic fibrosis
  • Diabetes
  • Epithelia
  • P2X receptors
  • Polycystic kidney disease
  • Sensors
  • Zinc
  • β cells

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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