Identification of an external divalent cation-binding site in the pore of a cGMP-activated channel.
Divalent cation blockade of cGMP-gated channels in photoreceptor cells ensures the low open channel noise required for a highly sensitive visual transduction process. This study identifies a divalent cation-binding site in the pore of a retinal cGMP-gated channel expressed in Xenopus oocytes. Substitution of a specific glutamate residue by a neutral amino acid renders the channel insensitive to external Mg2+ and Ca2+ and affects the conduction of Na+. The mutated channels remain sensitive to internal divalent cations. These results place the glutamate residue in the ion conduction pathway close to the extracellular surface.
Root
M J
MJ
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.
MacKinnon
R
R
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002413:Cations, Divalent / Q000378:metabolism* / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D004594:Electrophysiology; D007473:Ion Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D014981:Xenopus
D002413:Cations, Divalent; D007473:Ion Channels; D006152:Cyclic GMP