Na+/Cl- dipole couples agonist binding to kainate receptor activation.

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Wong AY, MacLean DM, Bowie D

Na+/Cl- dipole couples agonist binding to kainate receptor activation.

J Neurosci. 2007 Jun 20;27(25):6800-9.

PubMed ID

17581967 [ View in PubMed

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Abstract

Kainate-selective ionotropic glutamate receptors (GluRs) require external Na+ and Cl- as well as the neurotransmitter L-glutamate for activation. Although, external anions and cations apparently coactivate kainate receptors (KARs) in an identical manner, it has yet to be established how ions of opposite charge achieve this. An additional complication is that KARs are subject to other forms of cation modulation via extracellular acidification (i.e., protons) and divalent ions. Consequently, other cation species may compete with Na+ to regulate the time KARs remain in the open state. Here we designed experiments to unravel how external ions regulate GluR6 KARs. We show that GluR6 kinetics are unaffected by alterations in physiological pH but that divalent and alkali metal ions compete to determine the time course of KAR channel activity. Additionally, Na+ and Cl- ions coactivate GluR6 receptors by establishing a dipole, accounting for their common effect on KARs. Using charged amino acids as tethered ions, we further demonstrate that the docking order is fixed with cations binding first, followed by anions. Together, our findings identify the dipole as a novel gating feature that couples neurotransmitter binding to KAR activation.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Glutamic acid	Glutamate receptor ionotropic, kainate 2	Protein	Humans	Unknown	Not Available	Details