ArticlePLoS computational biology2018
Activation gating in HCN2 channels.
Article in PLoS computational biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Structure mirroring function: What's the 'matter' with the funny current?The Journal of physiology · 2026Review
- HCN1 is a primary HCN Pacemaker Channel in Neurons.Nature communications · 2026Article
- Towards a unified gating scheme for the CNBD ion channel family.The Journal of general physiology · 2026Review
- Membrane lipid nanodomains modulate HCN pacemaker channels in nociceptor DRG neurons.Nature communications · 2024Article
- The Dysfunction of CaInternational journal of molecular sciences · 2023Review
- Enlightening activation gating in P2X receptors.Purinergic signalling · 2022Review
- Unravelling the intricate cooperativity of subunit gating in P2X2 ion channels.Scientific reports · 2020Article
- The HCN domain is required for HCN channel cell-surface expression and couples voltage- and cAMP-dependent gating mechanisms.The Journal of biological chemistry · 2020Article
- Voltage vs. Ligand I: Structural basis of the intrinsic flexibility of S3 segment and its significance in ion channel activation.Channels (Austin, Tex.) · 2019Article
- Helix breaking transition in the S4 of HCN channel is critical for hyperpolarization-dependent gating.eLife · 2019Article
- Article
- HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons.eLife · 2019Article
- All four subunits of HCN2 channels contribute to the activation gating in an additive but intricate manner.The Journal of general physiology · 2018Article
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels control electrical rhythmicity in specialized brain and heart cells. We quantitatively analysed voltage-dependent activation of homotetrameric HCN2 channels and its modulation by the second messenger cAMP using global fits of hidden Markovian models to complex experimental data. We show that voltage-dependent activation is essentially governed by two separable voltage-dependent steps followed by voltage-independent opening of the pore. According to this model analysis, the binding of cAMP to the channels exerts multiple effects on the voltage-dependent gating: It stabilizes the open pore, reduces the total gating charge from ~8 to ~5, makes an additional closed state outside the activation pathway accessible and strongly accelerates the ON-gating but not the OFF-gating. Furthermore, the open channel has a much slower computed OFF-gating current than the closed channel, in both the absence and presence of cAMP. Together, these results provide detailed new insight into the voltage- and cAMP-induced activation gating of HCN channels.
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