Gating at the selectivity filter in cyclic nucleotide-gated channels

Jorge Contreras, Deepa Srikumar, Miguel Holmgren

Research output: Contribution to journalArticle

59 Citations (Scopus)

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 (KV) 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.

Original languageEnglish (US)
Pages (from-to)3310-3314
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number9
DOIs
StatePublished - Mar 4 2008

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Cyclic Nucleotide-Gated Cation Channels
Ions
Potassium Channels
Cadmium
Silver
Cysteine

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Ion channel
  • Signal transduction
  • cGMP

Cite this

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Gating at the selectivity filter in cyclic nucleotide-gated channels. / Contreras, Jorge; Srikumar, Deepa; Holmgren, Miguel.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 9, 04.03.2008, p. 3310-3314.

Research output: Contribution to journalArticle

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T1 - Gating at the selectivity filter in cyclic nucleotide-gated channels

AU - Contreras, Jorge

AU - Srikumar, Deepa

AU - Holmgren, Miguel

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AB - 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 (KV) 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.

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