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Nat Commun. 2013;4:2866. doi: 10.1038/ncomms3866.

Hysteresis of ligand binding in CNGA2 ion channels.

Author information

1
Institut für Physiologie II, Universitätsklinikum Jena, Friedrich-Schiller-Universität Jena, 07743 Jena, Germany.

Abstract

Tetrameric cyclic nucleotide-gated (CNG) channels mediate receptor potentials in olfaction and vision. The channels are activated by the binding of cyclic nucleotides to a binding domain embedded in the C terminus of each subunit. Here using a fluorescent cGMP derivative (fcGMP), we show for homotetrameric CNGA2 channels that ligand unbinding is ~50 times faster at saturating than at subsaturating fcGMP. Analysis with complex Markovian models reveals two pathways for ligand unbinding; the partially liganded open channel unbinds its ligands from closed states only, whereas the fully liganded channel reaches a different open state from which it unbinds all four ligands rapidly. Consequently, the transition pathways for ligand binding and activation of a fully liganded CNGA2 channel differ from that of ligand unbinding and deactivation, resulting in pronounced hysteresis of the gating mechanism. This concentration-dependent gating mechanism allows the channels to respond to changes in the cyclic nucleotide concentration with different kinetics.

PMID:
24287615
PMCID:
PMC3868267
DOI:
10.1038/ncomms3866
[Indexed for MEDLINE]
Free PMC Article

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