title: Physical basis of apparent pore dilation of ATP-activated P2X receptor channels.
abstract: 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.
authors.affiliation: Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Mufeng
authors.initials: M
authors.lastname: Li
authors.affiliation: Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Gilman E S
authors.initials: GE
authors.lastname: Toombes
authors.affiliation: Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Shai D
authors.initials: SD
authors.lastname: Silberberg
authors.affiliation: Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kenton J
authors.initials: KJ
authors.lastname: Swartz
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D058469:Receptors, Purinergic P2X / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000502:physiology
chemical_list: D058469:Receptors, Purinergic P2X; D050051:Transient Receptor Potential Channels; D000255:Adenosine Triphosphate