ArticleAmerican journal of physiology. Cell physiology2010
Ceramide modulates HERG potassium channel gating by translocation into lipid rafts.
Article in American journal of physiology. Cell physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Integrating AI and Molecular Modeling for Structural Prediction of a Closed-Pore State of the hERG Channel.Journal of chemical information and modeling · 2026Article
- Effect of the Membrane Environment on Pharmacologic Inhibition of hERG KJACC. Clinical electrophysiology · 2025Article
- Novel insights into the modulation of the voltage-gated potassium channel KJournal of lipid research · 2024Article
- Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases.International journal of molecular sciences · 2023Review
- High spatial density is associated with non-conducting Kv channels from two families.Biophysical journal · 2022Article
- Sphingolipid metabolism and signaling in cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Review
- Lipid regulation of hERG1 channel function.Nature communications · 2021Article
- Article
- Allosteric Coupling Between Drug Binding and the Aromatic Cassette in the Pore Domain of the hERG1 Channel: Implications for a State-Dependent Blockade.Frontiers in pharmacology · 2020Article
- Digging into Lipid Membrane Permeation for Cardiac Ion Channel Blocker d-Sotalol with All-Atom Simulations.Frontiers in pharmacology · 2018Article
- Implications of Human Transient Receptor Potential Melastatin 8 (TRPM8) Channel Gating from Menthol Binding Studies of the Sensing Domain.Biochemistry · 2016Article
- Altering sphingolipid composition with aging induces contractile dysfunction of gastric smooth muscle via K(Ca) 1.1 upregulation.Aging cell · 2015Article
- Lipid metabolites and their differential pro-arrhythmic profiles: of importance in the development of a new anti-arrhythmic pharmacology.Molecular and cellular biochemistry · 2014Review
- Article
- Annexins as organizers of cholesterol- and sphingomyelin-enriched membrane microdomains in Niemann-Pick type C disease.Cellular and molecular life sciences : CMLS · 2012Review
- Treating atopic dermatitis: safety, efficacy, and patient acceptability of a ceramide hyaluronic acid emollient foam.Clinical, cosmetic and investigational dermatology · 2012Article
- Sig1R protein regulates hERG channel expression through a post-translational mechanism in leukemic cells.The Journal of biological chemistry · 2011Article
- Insulin signaling in retinal neurons is regulated within cholesterol-enriched membrane microdomains.American journal of physiology. Endocrinology and metabolism · 2011Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Human ether-à-go-go-related gene (HERG) potassium channels play an important role in cardiac action potential repolarization, and HERG dysfunction can cause cardiac arrhythmias. However, recent evidence suggests a role for HERG in the proliferation and progression of multiple types of cancers, making it an attractive target for cancer therapy. Ceramide is an important second messenger of the sphingolipid family, which due to its proapoptotic properties has shown promising results in animal models as an anticancer agent. Yet the acute effects of ceramide on HERG potassium channels are not known. In the present study we examined the effects of cell-permeable C(6)-ceramide on HERG potassium channels stably expressed in HEK-293 cells. C(6)-ceramide (10 microM) reversibly inhibited HERG channel current (I(HERG)) by 36 +/- 5%. Kinetically, ceramide induced a significant hyperpolarizing shift in the current-voltage relationship (DeltaV(1/2) = -8 +/- 0.5 mV) and increased the deactivation rate (43 +/- 3% for tau(fast) and 51 +/- 3% for tau(slow)). Mechanistically, ceramide recruited HERG channels within caveolin-enriched lipid rafts. Cholesterol depletion and repletion experiments and mathematical modeling studies confirmed that inhibition and gating effects are mediated by separate mechanisms. The ceramide-induced hyperpolarizing gating shift (raft mediated) could offset the impact of inhibition (raft independent) during cardiac action potential repolarization, so together they may nullify any negative impact on cardiac rhythm. Our results provide new insights into the effects of C(6)-ceramide on HERG channels and suggest that C(6)-ceramide can be a promising therapeutic for cancers that overexpress HERG.
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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.