ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
PIP2-mediated HCN3 channel gating is crucial for rhythmic burst firing in thalamic intergeniculate leaflet neurons.
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 23 papers.
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23 citing papers in PubMed, 43 citations in OpenAlex.
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- Bibliometric analysis of hyperpolarization-activated cyclic nucleotide-gated (HCN)channels research (2004-2020).Channels (Austin, Tex.) · 2022Article
- The versatile regulation of K2P channels by polyanionic lipids of the phosphoinositide and fatty acid metabolism.The Journal of general physiology · 2022Article
- Computational Prediction of Phosphoinositide Binding to Hyperpolarization-Activated Cyclic-Nucleotide Gated Channels.Frontiers in physiology · 2022Article
- Review: HCN Channels in the Heart.Current cardiology reviews · 2022Review
- High-Frequency Neuronal Bursting is Essential for Circadian and Sleep Behaviors inThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels.Frontiers in molecular neuroscience · 2021Review
- CK2 Inhibition Prior to Status Epilepticus Persistently Enhances KFrontiers in cellular neuroscience · 2020Article
- Phosphoinositol metabolism affects AMP kinase-dependent K-ATP currents in rat substantia nigra dopamine neurons.Brain research · 2019Article
- Medullary Respiratory Circuit Is Reorganized by a Seasonally-Induced Program in Preparation for Hibernation.Frontiers in neuroscience · 2019Article
- HCN Channels: New Therapeutic Targets for Pain Treatment.Molecules (Basel, Switzerland) · 2018Review
- Disturbed Processing of Contextual Information in HCN3 Channel Deficient Mice.Frontiers in molecular neuroscience · 2017Article
- Two types of interneurons in the mouse lateral geniculate nucleus are characterized by different h-current density.Scientific reports · 2016Article
- The role of two-pore-domain background K⁺ (K₂p) channels in the thalamus.Pflugers Archiv : European journal of physiology · 2015Review
- HCN channels--modulators of cardiac and neuronal excitability.International journal of molecular sciences · 2015Review
- Estrous cycle plasticity in the hyperpolarization-activated current ih is mediated by circulating 17β-estradiol in preoptic area kisspeptin neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- HCN4 subunit expression in fast-spiking interneurons of the rat spinal cord and hippocampus.Neuroscience · 2013Article
- Learning-related synaptic growth mediated by internalization of Aplysia cell adhesion molecule is controlled by membrane phosphatidylinositol 4,5-bisphosphate synthetic pathway.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Targeted deletion of Kcne2 impairs HCN channel function in mouse thalamocortical circuits.PloS one · 2012Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels generate a pacemaking current, I(h), which regulates neuronal excitability and oscillatory activity in the brain. Although all four HCN isoforms are expressed in the brain, the functional contribution of HCN3 is unknown. Using immunohistochemistry, confocal microscopy, and whole-cell patch-clamp recording techniques, we investigated HCN3 function in thalamic intergeniculate leaflet (IGL) neurons, as HCN3 is reportedly preferentially expressed in these cells. We observed that I(h) recorded from IGL, but not ventral geniculate nucleus, neurons in HCN2(+/+) mice and rats activated slowly and were cAMP insensitive, which are hallmarks of HCN3 channels. We also observed strong immunolabeling for HCN3, with no labeling for HCN1 and HCN4, and only very weak labeling for HCN2. Deletion of HCN2 did not alter I(h) characteristics in mouse IGL neurons. These data together indicate that the HCN3 channel isoform generated I(h) in IGL neurons. Intracellular phosphatidylinositol-4,5-bisphosphate (PIP(2)) shifted I(h) activation to more depolarized potentials and accelerated activation kinetics. Upregulation of HCN3 function by PIP(2) augmented low-threshold burst firing and spontaneous oscillations; conversely, depletion of PIP(2) or pharmacologic block of I(h) resulted in a profound inhibition of excitability. The results indicate that functional expression of HCN3 channels in IGL neurons is crucial for intrinsic excitability and rhythmic burst firing, and PIP(2) serves as a powerful modulator of I(h)-dependent properties via an effect on HCN3 channel gating. Since the IGL is a major input to the suprachiasmatic nucleus, regulation of pacemaking function by PIP(2) in the IGL may influence sleep and circadian rhythms.
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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.