ArticleBritish journal of pharmacology2008
Effects of MiRP1 and DPP6 beta-subunits on the blockade induced by flecainide of Kv4.3/KChIP2 channels.
Article in British journal of pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Kir2.1 mutations differentially increase the risk of flecainide proarrhythmia in Andersen Tawil Syndrome.medRxiv : the preprint server for health sciences · 2024Article
- AKT and ERK1/2 activation via remote ischemic preconditioning prevents Kcne2-dependent sudden cardiac death.Physiological reports · 2019Article
- Identification of IQM-266, a Novel DREAM Ligand That Modulates KFrontiers in molecular neuroscience · 2019Article
- Regulation of Kv4.3 and hERG potassium channels by KChIP2 isoforms and DPP6 and response to the dual KBiochemical pharmacology · 2018Article
- Murine Electrophysiological Models of Cardiac Arrhythmogenesis.Physiological reviews · 2017Review
- Hydrogen Sulfide Targets the Cys320/Cys529 Motif in Kv4.2 to Inhibit the Ito Potassium Channels in Cardiomyocytes and Regularizes Fatal Arrhythmia in Myocardial Infarction.Antioxidants & redox signaling · 2015Article
- Cardiac and renal inward rectifier potassium channel pharmacology: emerging tools for integrative physiology and therapeutics.Current opinion in pharmacology · 2014Review
- Arrhythmogenic KCNE gene variants: current knowledge and future challenges.Frontiers in genetics · 2014Review
- Functional Characterization of Human Stem Cell-Derived Cardiomyocytes.Current protocols in pharmacology · 2014Article
- Sodium current deficit and arrhythmogenesis in a murine model of plakophilin-2 haploinsufficiency.Cardiovascular research · 2012Article
- A-type K+ currents in intralaminar thalamocortical relay neurons.Pflugers Archiv : European journal of physiology · 2011Article
- Effect of the I(to) activator NS5806 on cloned K(V)4 channels depends on the accessory protein KChIP2.British journal of pharmacology · 2010Article
- Propranolol regulates cardiac transient outward potassium channel in rat myocardium via cAMP/PKA after short-term but not after long-term ischemia.Naunyn-Schmiedeberg's archives of pharmacology · 2010Article
- Effect of salicylate on KCNQ4 of the guinea pig outer hair cell.Journal of neurophysiology · 2010Article
- KCNE2 modulation of Kv4.3 current and its potential role in fatal rhythm disorders.Heart rhythm · 2010Article
- The transmembrane beta-subunits KCNE1, KCNE2, and DPP6 modify pharmacological effects of the antiarrhythmic agent tedisamil on the transient outward current Ito.Naunyn-Schmiedeberg's archives of pharmacology · 2009Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe human cardiac transient outward potassium current (Ito) is believed to be composed of the pore-forming Kv4.3 alpha-subunit, coassembled with modulatory beta-subunits as KChIP2, MiRP1 and DPP6 proteins. beta-Subunits can alter the pharmacological response of Ito; therefore, we analysed the effects of flecainide on Kv4.3/KChIP2 channels coassembled with MiRP1 and/or DPP6 beta-subunits. EXPERIMENTAL APPROACH: Currents were recorded in Chinese hamster ovary cells stably expressing K(V)4.3/KChIP2 channels, and transiently transfected with either MiRP1, DPP6 or both, using the whole-cell patch-clamp technique. KEY
resultsIn control conditions, Kv4.3/KChIP2/MiRP1 channels exhibited the slowest activation and inactivation kinetics and showed an 'overshoot' in the time course of recovery from inactivation. The midpoint values (Vh) of the activation and inactivation curves for Kv4.3/KChIP2/DPP6 and Kv4.3/KChIP2/MiRP1/DPP6 channels were approximately 10 mV more negative than Vh values for Kv4.3/KChIP2 and Kv4.3/KChIP2/MiRP1 channels. Flecainide (0.1-100 microM) produced a similar concentration-dependent blockade of total integrated current flow (IC50 approximately 10 microM) in all the channel complexes. However, the IC50 values for peak current amplitude and inactivated channel block were significantly different. Flecainide shifted the Vh values of both the activation and inactivation curves to more negative potentials and apparently accelerated inactivation kinetics in all channels. Moreover, flecainide slowed recovery from inactivation in all the channel complexes and suppressed the 'overshoot' in Kv4.3/KChIP2/MiRP1 channels. CONCLUSIONS AND IMPLICATIONS: Flecainide directly binds to the Kv4.3 alpha-subunit when the channels are in the open and inactivated state and the presence of the beta-subunits modulates the blockade by altering the gating function.
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