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Naunyn Schmiedebergs Arch Pharmacol
2003 Mar 01;3673:281-8. doi: 10.1007/s00210-002-0672-5.
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Effects of the chromanol HMR 1556 on potassium currents in atrial myocytes.
Bosch RF
,
Schneck AC
,
Csillag S
,
Eigenberger B
,
Gerlach U
,
Brendel J
,
Lang HJ
,
Mewis C
,
Gögelein H
,
Seipel L
,
Kühlkamp V
.
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The chromanol HMR 1556 is a potent blocker of KvLQT1/minK potassium channels expressed in Xenopus oocytes. The compound is therefore a new class III antiarrhythmic drug with a distinct mechanism of action. However, the effect of HMR 1556 on atrial ion channels and the selectivity of block in the human heart has not been investigated. We tested the effects of HMR 1556 on repolarizing potassium currents in human and guinea pig atrial myocytes. Single atrial myocytes were isolated by enzymatic dissociation. Atrial potassium currents (I(Ks), I(Kr), in guinea pig, I(to), I(Kur), I(K1) in humans) were recorded at 36 degrees C in the whole cell mode of the patch clamp technique. HMR 1556 produced a concentration-dependent and reversible block of I(Ks) with a half maximal concentration (EC(50)) of 6.8 nmol/l. 10 micromol/l HMR 1556 almost completely inhibited I(Ks) (97.2+/-3.2%, n=6). Steady-state activation as well as kinetic properties of the current were not altered by HMR 1556. I(Kr) currents were not affected up to concentrations of 10 micromol/l. HMR 1556 did not inhibit other potassium currents in human atrium: I(to), I(Kur) and the classical inward rectifier potassium current I(K1) were not significantly affected up to concentrations that completely blocked I(Ks) (10 micromol/l). HMR 1556 is a highly-potent blocker of I(Ks) channels without exerting effects on other potassium currents involved in atrial repolarization. Given the potential advantages of I(Ks) vs. I(Kr) blockade, the drug's new mechanism of action warrants further investigation to clarify its role as an antiarrhythmic agent.
Barry,
Differential expression of voltage-gated K+ channel subunits in adult rat heart. Relation to functional K+ channels?
1995, Pubmed
Barry,
Differential expression of voltage-gated K+ channel subunits in adult rat heart. Relation to functional K+ channels?
1995,
Pubmed
Bauer,
Rate- and site-dependent effects of propafenone, dofetilide, and the new I(Ks)-blocking agent chromanol 293b on individual muscle layers of the intact canine heart.
1999,
Pubmed
Bosch,
Ambasilide prolongs the action potential and blocks multiple potassium currents in human atrium.
1999,
Pubmed
Bosch,
Effects of the chromanol 293B, a selective blocker of the slow, component of the delayed rectifier K+ current, on repolarization in human and guinea pig ventricular myocytes.
1998,
Pubmed
,
Xenbase
Bosch,
Electrophysiological mechanisms by which hypothyroidism delays repolarization in guinea pig hearts.
1999,
Pubmed
Busch,
Inhibition of IKs in guinea pig cardiac myocytes and guinea pig IsK channels by the chromanol 293B.
1996,
Pubmed
,
Xenbase
Crumb,
Description of a nonselective cation current in human atrium.
1995,
Pubmed
Fedida,
Identity of a novel delayed rectifier current from human heart with a cloned K+ channel current.
1993,
Pubmed
Feng,
Antisense oligodeoxynucleotides directed against Kv1.5 mRNA specifically inhibit ultrarapid delayed rectifier K+ current in cultured adult human atrial myocytes.
1997,
Pubmed
Freeman,
Expression of a minimal K+ channel protein in mammalian cells and immunolocalization in guinea pig heart.
1993,
Pubmed
,
Xenbase
Gerlach,
Synthesis and activity of novel and selective I(Ks)-channel blockers.
2001,
Pubmed
,
Xenbase
Gintant,
Two components of delayed rectifier current in canine atrium and ventricle. Does IKs play a role in the reverse rate dependence of class III agents?
1996,
Pubmed
Gögelein,
Inhibition of IKs channels by HMR 1556.
2000,
Pubmed
,
Xenbase
Hondeghem,
Class III antiarrhythmic agents have a lot of potential but a long way to go. Reduced effectiveness and dangers of reverse use dependence.
1990,
Pubmed
Jurkiewicz,
Rate-dependent prolongation of cardiac action potentials by a methanesulfonanilide class III antiarrhythmic agent. Specific block of rapidly activating delayed rectifier K+ current by dofetilide.
1993,
Pubmed
Li,
Evidence for two components of delayed rectifier K+ current in human ventricular myocytes.
1996,
Pubmed
Lynch,
Antiarrhythmic efficacy of selective blockade of the cardiac slowly activating delayed rectifier current, I(Ks), in canine models of malignant ischemic ventricular arrhythmia.
1999,
Pubmed
Lynch,
Comparison of binding to rapidly activating delayed rectifier K+ channel, IKr, and effects on myocardial refractoriness for class III antiarrhythmic agents.
1995,
Pubmed
Majumder,
Molecular cloning and functional expression of a novel potassium channel beta-subunit from human atrium.
1995,
Pubmed
,
Xenbase
Nattel,
Cardiac ultrarapid delayed rectifiers: a novel potassium current family o f functional similarity and molecular diversity.
1999,
Pubmed
Nattel,
The molecular and ionic specificity of antiarrhythmic drug actions.
1999,
Pubmed
Nattel,
Effects of the novel antiarrhythmic agent azimilide on experimental atrial fibrillation and atrial electrophysiologic properties.
1998,
Pubmed
Page,
Antiarrhythmic effects of azimilide in paroxysmal supraventricular tachycardia: efficacy and dose-response.
2002,
Pubmed
Pritchett,
Antiarrhythmic effects of azimilide in atrial fibrillation: efficacy and dose-response. Azimilide Supraventricular Arrhythmia Program 3 (SVA-3) Investigators.
2000,
Pubmed
Roden,
Current status of class III antiarrhythmic drug therapy.
1993,
Pubmed
Sanguinetti,
Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents.
1990,
Pubmed
Sanguinetti,
Delayed rectifier outward K+ current is composed of two currents in guinea pig atrial cells.
1991,
Pubmed
Singh,
Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: the symptomatic atrial fibrillation investigative research on dofetilide (SAFIRE-D) study.
2000,
Pubmed
Singh,
A third class of anti-arrhythmic action. Effects on atrial and ventricular intracellular potentials, and other pharmacological actions on cardiac muscle, of MJ 1999 and AH 3474.
1970,
Pubmed
Splawski,
Mutations in the hminK gene cause long QT syndrome and suppress IKs function.
1997,
Pubmed
,
Xenbase
Stambler,
Comparative efficacy of intravenous ibutilide versus procainamide for enhancing termination of atrial flutter by atrial overdrive pacing.
1996,
Pubmed
Stambler,
Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Ibutilide Repeat Dose Study Investigators.
1996,
Pubmed
Torp-Pedersen,
Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group.
1999,
Pubmed
Wang,
Comparative mechanisms of antiarrhythmic drug action in experimental atrial fibrillation. Importance of use-dependent effects on refractoriness.
1993,
Pubmed
Wang,
Rapid and slow components of delayed rectifier current in human atrial myocytes.
1994,
Pubmed
Wang,
Class III antiarrhythmic drug action in experimental atrial fibrillation. Differences in reverse use dependence and effectiveness between d-sotalol and the new antiarrhythmic drug ambasilide.
1994,
Pubmed
Wang,
Sustained depolarization-induced outward current in human atrial myocytes. Evidence for a novel delayed rectifier K+ current similar to Kv1.5 cloned channel currents.
1993,
Pubmed
Wang,
Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias.
1996,
Pubmed
Wang,
Comparison of binding and block produced by alternatively spliced Kvbeta1 subunits.
1996,
Pubmed
Wang,
Delayed rectifier outward current and repolarization in human atrial myocytes.
1993,
Pubmed
Yang,
Ibutilide, a methanesulfonanilide antiarrhythmic, is a potent blocker of the rapidly activating delayed rectifier K+ current (IKr) in AT-1 cells. Concentration-, time-, voltage-, and use-dependent effects.
1995,
Pubmed
Yue,
Transient outward and delayed rectifier currents in canine atrium: properties and role of isolation methods.
1996,
Pubmed