Physical basis of apparent pore dilation of ATP-activated P2X receptor channels

Nat Neurosci. 2015 Nov;18(11):1577-83. doi: 10.1038/nn.4120. Epub 2015 Sep 21.


The selectivity of ion channels is fundamental for their roles in electrical and chemical signaling and in ion homeostasis. Although most ion channels exhibit stable ion selectivity, the prevailing view of purinergic P2X receptor channels, transient receptor potential V1 (TRPV1) channels and acid-sensing ion channels (ASICs) is that their ion conduction pores dilate upon prolonged activation. We investigated this mechanism in P2X receptors and found that the hallmark shift in equilibrium potential observed with prolonged channel activation does not result from pore dilation, but from time-dependent alterations in the concentration of intracellular ions. We derived a physical model to calculate ion concentration changes during patch-clamp recordings, which validated our experimental findings and provides a quantitative guideline for effectively controlling ion concentration. Our results have fundamental implications for understanding ion permeation and gating in P2X receptor channels, as well as more broadly for using patch-clamp techniques to study ion channels and neuronal excitability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Cell Line
  • Humans
  • Ion Channel Gating / drug effects*
  • Ion Channel Gating / physiology
  • Membrane Potentials / drug effects*
  • Patch-Clamp Techniques / methods
  • Receptors, Purinergic P2X / metabolism*
  • Transient Receptor Potential Channels / physiology


  • Receptors, Purinergic P2X
  • Transient Receptor Potential Channels
  • Adenosine Triphosphate