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Related Experiment Videos

Ionic effects on human recombinant P2X7 receptor function.

A D Michel1, I P Chessell, P P Humphrey

  • 1Glaxo Institute of Applied Pharmacology, Department of Pharmacology, University of Cambridge, UK. ADM7393@GlaxoWellcome.co.uk

Naunyn-Schmiedeberg'S Archives of Pharmacology
|February 27, 1999
PubMed
Summary
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Monovalent and divalent ions significantly impact P2X7 receptor function. Physiological ion concentrations, including sodium and chloride, contribute to ATP

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Ion Channel Research

Background:

  • The P2X7 receptor is a key ion channel involved in cellular responses.
  • Understanding the influence of ions on P2X7 receptor activity is crucial for its pharmacological targeting.
  • Previous studies have indicated potential modulation of P2X7 receptor by various ions.

Purpose of the Study:

  • To investigate the effects of monovalent and divalent ions on the human recombinant P2X7 receptor.
  • To determine how different ion concentrations and types modulate the receptor's response to the agonist DbATP.
  • To elucidate the role of physiological ion concentrations in regulating P2X7 receptor potency.

Main Methods:

  • HEK293 cells expressing the human P2X7 receptor were utilized.

Related Experiment Videos

  • The effect of the P2 receptor agonist, 2'- and 3'-O-(4-benzoyl-benzoyl)-ATP (DbATP), on YO-PRO-1 dye uptake was measured.
  • Electrophysiological studies were conducted to confirm findings on ion effects.

    • Main Results:

    • Both calcium and magnesium ions decreased the potency of DbATP.
    • P2X7 receptor potency was sensitive to pH, with optimal activity at pH 7.5.
    • Monovalent ions significantly altered DbATP potency; for example, NaCl-free buffer increased potency 19-fold compared to NaCl buffer.
    • Specific monovalent cations (choline, potassium, sodium) and anions (aspartate, glutamate, chloride, iodide) differentially affected DbATP potency.
    • Electrophysiology confirmed that monovalent anions inhibit P2X7 receptor function.

    Conclusions:

    • P2X7 receptor function is markedly affected by a broad spectrum of ions.
    • Physiological concentrations of sodium, chloride, and divalent cations contribute to the observed low potency of ATP as a P2X7 receptor agonist.
    • These findings highlight the importance of ionic environment in P2X7 receptor pharmacology.