ArticleThe Journal of general physiology2013
Binding of the auxiliary subunit TRIP8b to HCN channels shifts the mode of action of cAMP.
Article in The Journal of general physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- Reward-associated cues reduce H-current amplitude in midbrain dopamine neurons.Neuropharmacology · 2025Article
- Anisotropic Network Analysis of Open/Closed HCN4 Channel Advocates Asymmetric Subunit Cooperativity in cAMP Modulation of Gating.Journal of chemical information and modeling · 2024Article
- A high affinity switch for cAMP in the HCN pacemaker channels.Nature communications · 2024Article
- Article
- Validation of the binding stoichiometry between HCN channels and their neuronal regulator TRIP8b by single molecule measurements.Frontiers in physiology · 2022Article
- Regulation of HCN Channels by Protein Interactions.Frontiers in physiology · 2022Review
- Hippocampal cAMP regulates HCN channel function on two time scales with differential effects on animal behavior.Science translational medicine · 2021Article
- IProgress in biophysics and molecular biology · 2021Review
- Gating movements and ion permeation in HCN4 pacemaker channels.Molecular cell · 2021Article
- The structure and function of TRIP8b, an auxiliary subunit of hyperpolarization-activated cyclic-nucleotide gated channels.Channels (Austin, Tex.) · 2020Review
- Rational design of a mutation to investigate the role of the brain protein TRIP8b in limiting the cAMP response of HCN channels in neurons.The Journal of general physiology · 2020Article
- Article
- cyclic AMP Regulation and Its Command in the Pacemaker Channel HCN4.Frontiers in physiology · 2020Review
- Phosphorylation of the HCN channel auxiliary subunit TRIP8b is altered in an animal model of temporal lobe epilepsy and modulates channel function.The Journal of biological chemistry · 2019Article
- The VAMP-associated protein VAPB is required for cardiac and neuronal pacemaker channel function.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Store depletion-induced h-channel plasticity rescues a channelopathy linked to Alzheimer's disease.Neurobiology of learning and memory · 2018Article
- Exploiting natural regulation.eLife · 2018Article
- Article
- Modulation of thalamocortical oscillations by TRIP8b, an auxiliary subunit for HCN channels.Brain structure & function · 2018Article
- Structural insights into the mechanisms of CNBD channel function.The Journal of general physiology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Hyperpolarization-activated cyclic nucleotide-regulated cation (HCN) channels generate the hyperpolarization-activated cation current Ih present in many neurons. These channels are directly regulated by the binding of cAMP, which both shifts the voltage dependence of HCN channel opening to more positive potentials and increases maximal Ih at extreme negative voltages where voltage gating is complete. Here we report that the HCN channel brain-specific auxiliary subunit TRIP8b produces opposing actions on these two effects of cAMP. In the first action, TRIP8b inhibits the effect of cAMP to shift voltage gating, decreasing both the sensitivity of the channel to cAMP (K1/2) and the efficacy of cAMP (maximal voltage shift); conversely, cAMP binding inhibits these actions of TRIP8b. These mutually antagonistic actions are well described by a cyclic allosteric mechanism in which TRIP8b binding reduces the affinity of the channel for cAMP, with the affinity of the open state for cAMP being reduced to a greater extent than the cAMP affinity of the closed state. In a second apparently independent action, TRIP8b enhances the action of cAMP to increase maximal Ih. This latter effect cannot be explained by the cyclic allosteric model but results from a previously uncharacterized action of TRIP8b to reduce maximal current through the channel in the absence of cAMP. Because the binding of cAMP also antagonizes this second effect of TRIP8b, application of cAMP produces a larger increase in maximal Ih in the presence of TRIP8b than in its absence. These findings may provide a mechanistic explanation for the wide variability in the effects of modulatory transmitters on the voltage gating and maximal amplitude of Ih reported for different neurons in the brain.
Indexed as
Identifiers
What OpenQuestion holds
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.