title: Gating at the selectivity filter in cyclic nucleotide-gated channels.
abstract: By opening and closing the permeation pathway (gating) in response to cGMP binding, cyclic nucleotide-gated (CNG) channels serve key roles in the transduction of visual and olfactory signals. Compiling evidence suggests that the activation gate in CNG channels is not located at the intracellular end of pore, as it has been established for voltage-activated potassium (K(V)) channels. Here, we show that ion permeation in CNG channels is tightly regulated at the selectivity filter. By scanning the entire selectivity filter using small cysteine reagents, like cadmium and silver, we observed a state-dependent accessibility pattern consistent with gated access at the middle of the selectivity filter, likely at the corresponding position known to regulate structural changes in KcsA channels in response to low concentrations of permeant ions.
authors.affiliation: Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-3701, USA.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Contreras
authors.forename: Deepa
authors.initials: D
authors.lastname: Srikumar
authors.forename: Miguel
authors.initials: M
authors.lastname: Holmgren
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002104:Cadmium; D002460:Cell Line; D006152:Cyclic GMP; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D003545:Cysteine; D015640:Ion Channel Gating / Q000235:genetics*; D011487:Protein Conformation; D012834:Silver; D013379:Substrate Specificity; D014162:Transfection
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D002104:Cadmium; D012834:Silver; D006152:Cyclic GMP; D003545:Cysteine