title: Hysteresis of ligand binding in CNGA2 ion channels.
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.
authors.affiliation: Institut für Physiologie II, Universitätsklinikum Jena, Friedrich-Schiller-Universität Jena, 07743 Jena, Germany.
authors.forename: Vasilica
authors.initials: V
authors.lastname: Nache
authors.forename: Thomas
authors.initials: T
authors.lastname: Eick
authors.forename: Eckhard
authors.initials: E
authors.lastname: Schulz
authors.forename: Ralf
authors.initials: R
authors.lastname: Schmauder
authors.forename: Klaus
authors.initials: K
authors.lastname: Benndorf
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000737:chemistry / Q000378:metabolism*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D005260:Female; D007700:Kinetics; D008024:Ligands; D009865:Oocytes / Q000737:chemistry / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011485:Protein Binding; D029867:Xenopus Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000235:genetics / Q000378:metabolism*
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D008024:Ligands; D029867:Xenopus Proteins; D006152:Cyclic GMP