ArticleThe Journal of general physiology2006
Distinct populations of HCN pacemaker channels produce voltage-dependent and voltage-independent currents.
Article in The Journal of general physiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 56 citations in OpenAlex.
- Roles of funny HCN.Comparative biochemistry and physiology. Toxicology & pharmacology : CBP · 2025Review
- Similar voltage-sensor movement in spHCN channels can cause closing, opening, or inactivation.The Journal of general physiology · 2023Article
- Frequency-Dependent Properties of the Hyperpolarization-Activated Cation Current, IInternational journal of molecular sciences · 2022Article
- Gating movements and ion permeation in HCN4 pacemaker channels.Molecular cell · 2021Article
- Bidirectional flow of the funny current (IProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Photodynamic Modification of Native HCN Channels Expressed in Thalamocortical Neurons.ACS chemical neuroscience · 2020Article
- Singlet oxygen modification abolishes voltage-dependent inactivation of the sea urchin spHCN channel.The Journal of general physiology · 2018Article
- Kir2.1 channels set two levels of resting membrane potential with inward rectification.Pflugers Archiv : European journal of physiology · 2018Article
- Reduced Hyperpolarization-Activated Current Contributes to Enhanced Intrinsic Excitability in Cultured Hippocampal Neurons from PrP(-/-) Mice.Frontiers in cellular neuroscience · 2016Article
- Stress Impairs Prefrontal Cortical Function via D1 Dopamine Receptor Interactions With Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels.Biological psychiatry · 2015Article
- Activation of Ih and TTX-sensitive sodium current at subthreshold voltages during CA1 pyramidal neuron firing.Journal of neurophysiology · 2015Article
- Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- HCN2 channels: a permanent open state and conductance changes.The Journal of membrane biology · 2015Article
- State-dependent and site-directed photodynamic transformation of HCN2 channel by singlet oxygen.The Journal of general physiology · 2014Article
- cAMP control of HCN2 channel Mg2+ block reveals loose coupling between the cyclic nucleotide-gating ring and the pore.PloS one · 2014Article
- Depressed pacemaker activity of sinoatrial node myocytes contributes to the age-dependent decline in maximum heart rate.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Hyperpolarisation-activated cyclic nucleotide-gated channels regulate the spontaneous firing rate of olfactory receptor neurons and affect glomerular formation in mice.The Journal of physiology · 2013Article
- A leucine zipper motif essential for gating of hyperpolarization-activated channels.The Journal of biological chemistry · 2012Article
- HCN1 and HCN2 proteins are expressed in cochlear hair cells: HCN1 can form a ternary complex with protocadherin 15 CD3 and F-actin-binding filamin A or can interact with HCN2.The Journal of biological chemistry · 2012Article
- Charge movement in gating-locked HCN channels reveals weak coupling of voltage sensors and gate.The Journal of general physiology · 2012Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Hyperpolarization-activated HCN pacemaker channels are critical for the generation of spontaneous activity and the regulation of excitability in the heart and in many types of neurons. These channels produce both a voltage-dependent current (I(h)) and a voltage-independent current (I(inst) or VIC). In this study, we explored the molecular basis of the voltage-independent current. We found that for the spHCN isoform, VIC averaged approximately 4% of the maximum HCN conductance that could be activated by hyperpolarization. Cyclic AMP increased the voltage-independent current in spHCN to approximately 8% of maximum. In HCN2, VIC was approximately 2% of the maximal current, and was little affected by cAMP. VIC in both spHCN and HCN2 was blocked rapidly both by ZD7288 (an HCN channel blocker that is thought to bind in the conduction pore) and by application of Cd2+ to channels containing an introduced cysteine in the pore (spHCN-464C or HCN2-436C). These results suggest that VIC flows through the main conduction pathway, down the central axis of the protein. We suspected that VIC simply represented a nonzero limiting open probability for HCN channels at positive voltages. Surprisingly, we found instead that the spHCN channels carrying VIC were not in rapid equilibrium with the channels carrying the voltage-dependent current, because they could be blocked independently; a single application of blocker at a depolarized potential essentially eliminated VIC with little change in I(h). Thus, VIC appears to be produced by a distinct population of HCN channels. This voltage-independent current could contribute significantly to the role of HCN channels in neurons and myocytes; VIC flowing through the channels at physiological potentials would tend to promote excitability by accelerating both depolarization and repolarization.
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