ArticleProceedings of the National Academy of Sciences of the United States of America2005
The carboxyl-terminal region of cyclic nucleotide-modulated channels is a gating ring, not a permeation path.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 53 citations in OpenAlex.
- Structure mirroring function: What's the 'matter' with the funny current?The Journal of physiology · 2026Review
- Missing validation of key features in HCN single-channel recordings.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Gating movements and ion permeation in HCN4 pacemaker channels.Molecular cell · 2021Article
- Allosteric conformational change of a cyclic nucleotide-gated ion channel revealed by DEER spectroscopy.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Cytoplasmic Autoinhibition in HCN Channels is Regulated by the Transmembrane Region.The Journal of membrane biology · 2020Article
- The EAG Voltage-Dependent KFrontiers in pharmacology · 2020Review
- Patch-clamp fluorometry-based channel counting to determine HCN channel conductance.The Journal of general physiology · 2016Article
- Role of Dynamics in the Autoinhibition and Activation of the Hyperpolarization-activated Cyclic Nucleotide-modulated (HCN) Ion Channels.The Journal of biological chemistry · 2015Article
- The enigmatic cytoplasmic regions of KCNH channels.Journal of molecular biology · 2015Review
- A mechanism for the auto-inhibition of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel opening and its relief by cAMP.The Journal of biological chemistry · 2014Article
- cAMP control of HCN2 channel Mg2+ block reveals loose coupling between the cyclic nucleotide-gating ring and the pore.PloS one · 2014Article
- Structural correlates of selectivity and inactivation in potassium channels.Biochimica et biophysica acta · 2012Review
- Recessive loss-of-function mutation in the pacemaker HCN2 channel causing increased neuronal excitability in a patient with idiopathic generalized epilepsy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
- C-terminal dimerization activates the nociceptive transduction channel transient receptor potential vanilloid 1.The Journal of biological chemistry · 2011Article
- Structural basis for the channel function of a degraded ABC transporter, CFTR (ABCC7).The Journal of general physiology · 2011Article
- Preferential use of unobstructed lateral portals as the access route to the pore of human ATP-gated ion channels (P2X receptors).Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Ion access pathway to the transmembrane pore in P2X receptor channels.The Journal of general physiology · 2011Article
- Cytoplasmic cAMP-sensing domain of hyperpolarization-activated cation (HCN) channels uses two structurally distinct mechanisms to regulate voltage gating.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Cysteine 723 in the C-linker segment confers oxidative inhibition of hERG1 potassium channels.The Journal of physiology · 2010Article
- Structural changes in the cytoplasmic domain of the mechanosensitive channel MscS during opening.Biophysical journal · 2009Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The recent elucidation of the structure of the carboxyl-terminal region of the hyperpolarization-activated cyclic nucleotide-modulated (HCN2) channel has prompted us to investigate a curious feature of this structure in HCN2 channels and in the related CNGA1 cyclic nucleotide-gated (CNG) channels. The crystallized fragment of the HCN2 channel contains both the cyclic nucleotide-binding domain (CNBD) and the C-linker region, which connects the CNBD to the pore. At the center of the fourfold-symmetric structure is a tunnel that runs perpendicular to the membrane. The narrowest part of the tunnel is approximately 10 A in diameter and is lined by a ring of negatively charged amino acids: D487, E488, and D489. Many ion channels have "charge rings" that focus permeant ions at the mouth of the pore and increase channel conductance. We used nonstationary fluctuation analysis and single-channel recording, coupled with site-directed mutagenesis and cysteine modification, to determine whether this part of HCN and CNG channels might be an extension of the permeation pathway. Our results indicate that modifying charge-ring amino acids affects gating but not ion permeation in HCN2 and CNG channels. Thus, this portion of the channel is not an obligatory part of the ion path but instead acts as a "gating ring." The carboxyl-terminal region of these channels must hang below the pore much like the "hanging gondola" of voltage-gated potassium channels, but the permeation pathway must exit the protein before the level of the ring of charged amino acids.
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