ArticleBiochemistry2008
Caveolin-3 associates with and affects the function of hyperpolarization-activated cyclic nucleotide-gated channel 4.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The Contribution of HCN Channelopathies in Different Epileptic Syndromes, Mechanisms, Modulators, and Potential Treatment Targets: A Systematic Review.Frontiers in molecular neuroscience · 2022Pooled it
- A rare HCN4 variant combined with sick sinus syndrome, left ventricular noncompaction, and complex congenital heart disease.Channels (Austin, Tex.) · 2025Article
- Regulation of HCN Channels by Protein Interactions.Frontiers in physiology · 2022Review
- Review: HCN Channels in the Heart.Current cardiology reviews · 2022Review
- Structural and Electrical Remodeling of the Sinoatrial Node in Diabetes: New Dimensions and Perspectives.Frontiers in endocrinology · 2022Review
- Cardiac and neuronal HCN channelopathies.Pflugers Archiv : European journal of physiology · 2020Review
- Long QT syndrome caveolin-3 mutations differentially modulate KThe Journal of physiology · 2019Article
- Functional Microdomains in Heart's Pacemaker: A Step Beyond Classical Electrophysiology and Remodeling.Frontiers in physiology · 2018Review
- Caveolin-3 Microdomain: Arrhythmia Implications for Potassium Inward Rectifier and Cardiac Sodium Channel.Frontiers in physiology · 2018Review
- Murine Electrophysiological Models of Cardiac Arrhythmogenesis.Physiological reviews · 2017Review
- Coordinating heart morphogenesis: A novel role for hyperpolarization-activated cyclic nucleotide-gated (HCN) channels during cardiogenesis inCommunicative & integrative biology · 2017Article
- Sarcolemmal dependence of cardiac protection and stress-resistance: roles in aged or diseased hearts.British journal of pharmacology · 2016Review
- Electrophysiology and metabolism of caveolin-3-overexpressing mice.Basic research in cardiology · 2016Article
- Interaction of Caveolin-3 and HCN is involved in the pathogenesis of diabetic cystopathy.Scientific reports · 2016Article
- Exploring Human Diseases and Biological Mechanisms by Protein Structure Prediction and Modeling.Advances in experimental medicine and biology · 2016Article
- HCN Channels Modulators: The Need for Selectivity.Current topics in medicinal chemistry · 2016Review
- Pacemaker activity of the human sinoatrial node: an update on the effects of mutations in HCN4 on the hyperpolarization-activated current.International journal of molecular sciences · 2015Review
- Inhibition of cardiac pacemaker channel hHCN2 depends on intercalation of lipopolysaccharide into channel-containing membrane microdomains.The Journal of physiology · 2014Article
- Potential of caveolae in the therapy of cardiovascular and neurological diseases.Frontiers in physiology · 2014Article
- Signaling epicenters: the role of caveolae and caveolins in volatile anesthetic induced cardiac protection.Current pharmaceutical design · 2014Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Targeting of ion channels to caveolae, a subset of lipid rafts, allow cells to respond efficiently to extracellular signals. Hyperpolarization-activated cyclic nucleotide-gated channel (HCN) 4 is a major subunit for the cardiac pacemaker. Caveolin-3 (Cav3), abundantly expressed in muscle cells, is responsible for forming caveolae. P104L, a Cav3 mutant, has a dominant negative effect on wild type (WT) Cav3 and associates with limb-girdle muscular dystrophy and cardiomyopathy. HCN4 was previously shown to localize to lipid rafts, but how caveolae regulate the function of HCN4 is unknown. We hypothesize that Cav3 associates with HCN4 and regulates the function of HCN4 channel. In this study, we applied whole-cell patch clamp analysis, immunostaining, biotinylation, and immunoprecipitation methods to investigate this hypothesis. The immunoprecipitation results indicated an association of HCN4 and Cav3 in the heart and in HEK293 cells. Our immunostaining results showed that HCN4 colocalized with Cav3 but only partially colocalized with P104L in HEK293 cells. Transient expression of Cav3, but not P104L, in HEK 293 cells stably expressing HCN4 caused a 45% increase in HCN4 current (IHCN4) density. Transient expression of P104L caused a two-fold increase in the activation time constant for IHCN4 and shifted the voltage of the steady-state inactivation to a more negative potential. We conclude that HCN4 associates with Cav3 to form a HCN4 macromolecular complex. Our results indicated that disruption of caveolae using P104L alters HCN4 function and could cause a reduction of cardiac pacemaker activity.
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