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Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels
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Different sensitivities to pH of ATP-induced currents at four cloned P2X receptors

R Stoop1, A Surprenant, R A North

  • 1Geneva Biomedical Research Institute, Glaxo Wellcome Research and Development, Plan-les-Ouates, 1228 Geneva, Switzerland.

Journal of Neurophysiology
|October 27, 1997
PubMed

Insights

Extracellular pH significantly impacts ATP-induced currents in P2X receptors. Acidification inhibits P2X1, P2X3, and P2X4 receptors while potentiating P2X2 receptors, offering insights into neuronal signaling.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Adenosine triphosphate (ATP) acts as a signaling molecule in the central nervous system.
  • P2X receptors are ligand-gated ion channels activated by extracellular ATP.
  • Extracellular pH is a critical factor influencing cellular function and receptor activity.

Purpose of the Study:

  • To investigate the influence of extracellular pH on ATP-induced currents mediated by various P2X receptor subtypes.
  • To characterize the specific effects of pH changes on different P2X receptor subunits and their responses to ATP.
  • To explore the implications of pH-dependent P2X receptor activity for synaptic transmission and receptor identification.

Main Methods:

  • HEK293 cells were transfected with distinct P2X receptor subunits (P2X1, P2X2, P2X3, P2X4).
  • Electrophysiological recordings were performed to measure currents induced by ATP or alphabeta-methylene-ATP.
  • Extracellular pH was systematically altered to assess its effect on receptor activation and concentration-response relationships.

Main Results:

  • Acidification decreased ATP-induced currents in cells expressing P2X1, P2X3, and P2X4 receptors.
  • Acidification increased ATP-induced currents in cells expressing P2X2 receptors and heteromeric P2X2/P2X3 receptors.
  • P2X2 receptors showed a leftward shift in ATP concentration-response curve (pKa 7.3) with acidification, while P2X4 receptors exhibited a rightward shift (pKa 6.8).

Conclusions:

  • The activity of P2X receptors is significantly modulated by extracellular pH.
  • pH-dependent effects on P2X receptors have implications for understanding synaptic transmission.
  • This pH sensitivity can serve as a tool for molecularly identifying P2X receptors in the brain.

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