ArticleThe Journal of general physiology2005
Hysteresis in the voltage dependence of HCN channels: conversion between two modes affects pacemaker properties.
Article in The Journal of general physiology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 136 citations in OpenAlex.
- HCN1 is a primary HCN Pacemaker Channel in Neurons.Nature communications · 2026Article
- Dual block evidence of the effects of topiramate, a sulfamate-substituted monosaccharide, on voltage-gated sodium current and hyperpolarization-activated cation current.BMC pharmacology & toxicology · 2025Article
- Recent Advances in Ionic Mechanisms in Pituitary Cells: Implications for Electrophysiological and Electropharmacological Research.Journal of clinical medicine · 2025Review
- A rich conformational palette underlies human CaNature communications · 2025Article
- Different fluorescent labels report distinct components of spHCN channel voltage sensor movement.The Journal of general physiology · 2024Article
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- Loose Coupling between the Voltage Sensor and the Activation Gate in Mammalian HCN Channels Suggests a Gating Mechanism.International journal of molecular sciences · 2024Article
- Cannabidiol Modulates M-Type KBiomedicines · 2023Article
- Modulation of Voltage-Gating and Hysteresis of Lysenin Channels by CuInternational journal of molecular sciences · 2023Article
- Modulating Hyperpolarization-Activated Cation Currents through Small Molecule Perturbations: Magnitude and Gating Control.Biomedicines · 2023Review
- Vascular mechanotransduction.Physiological reviews · 2023Review
- Charge-voltage curves of Shaker potassium channel are not hysteretic at steady state.The Journal of general physiology · 2023Article
- Concerted suppressive effects of carisbamate, an anti-epileptic alkyl-carbamate drug, on voltage-gated NaFrontiers in cellular neuroscience · 2023Article
- Effective Perturbations by Small-Molecule Modulators on Voltage-Dependent Hysteresis of Transmembrane Ionic Currents.International journal of molecular sciences · 2022Review
- Paradigm shift: new concepts for HCN4 function in cardiac pacemaking.Pflugers Archiv : European journal of physiology · 2022Review
- Characterization of Inhibitory Capability on Hyperpolarization-Activated Cation Current Caused by Lutein (β,ε-Carotene-3,3'-Diol), a Dietary Xanthophyll Carotenoid.International journal of molecular sciences · 2022Article
- Evidence for Dual Activation ofInternational journal of molecular sciences · 2022Article
- Direct Regulation of Hyperpolarization-Activated Cyclic-Nucleotide Gated (HCN1) Channels by Cannabinoids.Frontiers in molecular neuroscience · 2022Article
- Effective Activation of BKPharmaceuticals (Basel, Switzerland) · 2021Article
- Effective Activation by Kynurenic Acid and Its Aminoalkylated Derivatives on M-Type KInternational journal of molecular sciences · 2021Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Hyperpolarization-activated, cyclic nucleotide-gated (HCN) ion channels are important for rhythmic activity in the brain and in the heart. In this study, using ionic and gating current measurements, we show that cloned spHCN channels undergo a hysteresis in their voltage dependence during normal gating. For example, both the gating charge versus voltage curve, Q(V), and the conductance versus voltage curve, G(V), are shifted by about +60 mV when measured from a hyperpolarized holding potential compared with a depolarized holding potential. In addition, the kinetics of the tail current and the activation current change in parallel to the voltage shifts of the Q(V) and G(V) curves. Mammalian HCN1 channels display similar effects in their ionic currents, suggesting that the mammalian HCN channels also undergo voltage hysteresis. We propose a model in which HCN channels transit between two modes. The voltage dependence in the two modes is shifted relative to each other, and the occupancy of the two modes depends on the previous activation of the channel. The shifts in the voltage dependence are fast (tau approximately 100 ms) and are not accompanied by any apparent inactivation. In HCN1 channels, the shift in voltage dependence is slower in a 100 mM K extracellular solution compared with a 1 mM K solution. Based on these findings, we suggest that molecular conformations similar to slow (C-type) inactivation of K channels underlie voltage hysteresis in HCN channels. The voltage hysteresis results in HCN channels displaying different voltage dependences during different phases in the pacemaker cycle. Computer simulations suggest that voltage hysteresis in HCN channels decreases the risk of arrhythmia in pacemaker cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.