ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Deletion of the hyperpolarization-activated cyclic nucleotide-gated channel auxiliary subunit TRIP8b impairs hippocampal Ih localization and function and promotes antidepressant behavior in mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 124 citations in OpenAlex.
- Ionic Homeostasis Failure in Major Depressive Disorder: Ion Channel Mechanisms, Excitation-Inhibition Imbalance, and Precision Therapeutics.International journal of molecular sciences · 2026Review
- Acute pretrauma ethanol exacerbates PTSD-like phenotype in rats and is reversed by early intranasal ketamine.Scientific reports · 2026Article
- Dorsal CA1 projections to nucleus accumbens and lateral septum differentially regulate social and locomotor behavior.Cerebral cortex (New York, N.Y. : 1991) · 2026Article
- Serotonergic psychedelic 5-MeO-DMT alters plasticity-related gene expression and generates anxiolytic effects in stressed mice.Molecular psychiatry · 2025Article
- Impaired touch sensation on hairy skin in HCN3-deficient mice.Frontiers in neuroscience · 2025Article
- Alzheimer's-linked axonal changes accompany elevated antidromic action potential failure rate in aged mice.Brain research · 2024Article
- Multiple Exposures to Sevoflurane General Anesthesia During Pregnancy Inhibit CaMKII/CREB Axis by Downregulating HCN2 to Induce an Autism-Like Phenotype in Offspring Mice.Journal of molecular neuroscience : MN · 2024Article
- Characterization of hyperpolarization-activated cyclic nucleotide-gated channels in oligodendrocytes.Frontiers in cellular neuroscience · 2024Article
- Inhibition of HCN1 currents by norquetiapine, an active metabolite of the atypical anti-psychotic drug quetiapine.Frontiers in pharmacology · 2024Article
- cAMP-mediated upregulation of HCN channels in VTA dopamine neurons promotes cocaine reinforcement.Molecular psychiatry · 2023Article
- Activation of metabotropic glutamate receptor 1 regulates hippocampal CA1 region excitability in rats with status epilepticus by suppressing the HCN1 channel.Neural regeneration research · 2023Article
- The Impact of Altered HCN1 Expression on Brain Function and Its Relationship with Epileptogenesis.Current neuropharmacology · 2023Review
- Antidepressant-like activity of a brain penetrant HCN channel inhibitor in mice.Frontiers in pharmacology · 2023Article
- Target deconvolution studies of (2R,6R)-hydroxynorketamine: an elusive search.Molecular psychiatry · 2022Article
- Glucocorticoid-glucocorticoid receptor-HCN1 channels reduce neuronal excitability in dorsal hippocampal CA1 neurons.Molecular psychiatry · 2022Article
- Discovery of a small-molecule inhibitor of the TRIP8b-HCN interaction with efficacy in neurons.The Journal of biological chemistry · 2022Article
- Identification of HCN1 as a 14-3-3 client.PloS one · 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
- Frontal cortex genetic ablation of metabotropic glutamate receptor subtype 3 (mGluNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
30 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 8 institutions in 3 countries.
Funding
Abstract
Output properties of neurons are greatly shaped by voltage-gated ion channels, whose biophysical properties and localization within axodendritic compartments serve to significantly transform the original input. The hyperpolarization-activated current, I(h), is mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and plays a fundamental role in influencing neuronal excitability by regulating both membrane potential and input resistance. In neurons such as cortical and hippocampal pyramidal neurons, the subcellular localization of HCN channels plays a critical functional role, yet mechanisms controlling HCN channel trafficking are not fully understood. Because ion channel function and localization are often influenced by interacting proteins, we generated a knock-out mouse lacking the HCN channel auxiliary subunit, tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b). Eliminating expression of TRIP8b dramatically reduced I(h) expression in hippocampal pyramidal neurons. Loss of I(h)-dependent membrane voltage properties was attributable to reduction of HCN channels on the neuronal surface, and there was a striking disruption of the normal expression pattern of HCN channels in pyramidal neuron dendrites. In heterologous cells and neurons, absence of TRIP8b increased HCN subunit targeting to and degradation by lysosomes. Mice lacking TRIP8b demonstrated motor learning deficits and enhanced resistance to multiple tasks of behavioral despair with high predictive validity for antidepressant efficacy. We observed similar resistance to behavioral despair in distinct mutant mice lacking HCN1 or HCN2. These data demonstrate that interaction with the auxiliary subunit TRIP8b is a major mechanism underlying proper expression of HCN channels and I(h) in vivo, and suggest that targeting I(h) may provide a novel approach to treatment of depression.
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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.