Class III Antiarrhythmic Effects of Zatebradine

Valenzuela, Carmen; Delpón, Eva; Franqueza, Laura; Pérez, Onésima; Tamargo, Juan; Snyders, Dirk J.

doi:10.1161/01.cir.94.3.562

Cited by 84 publications

(34 citation statements)

References 43 publications

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“…3). Furthermore, oxypeucedanin slowed the time course of deactivating tail currents, thus inducing the tail crossover phenomenon, which is typically detected for the open channel blocks 9,20) (Fig. 4).…”

Section: Discussionmentioning

confidence: 83%

“…The action potentials were recorded with a 3-M KClfilled microelectrode (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) connected to an amplifier (KS-700, WPI), and they were displayed on an oscilloscope (dual-beam storage 5113, Tektronix, Beaverton, OR, U.S.A.). The tracings on the oscilloscope screen were photographed using 35-mm film, and they also recorded on a chart recorder (RS 3400, Gould, Cleveland, OH, U.S.A.).…”

Section: Cell Isolation and Transfectionmentioning

confidence: 99%

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Effects of Oxypeucedanin on hKv1.5 and Action Potential Duration

Eun

Park

Choi

et al. 2005

Biological & Pharmaceutical Bulletin

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Section: Discussionmentioning

confidence: 83%

Section: Cell Isolation and Transfectionmentioning

confidence: 99%

Effects of Oxypeucedanin on hKv1.5 and Action Potential Duration

Eun

Park

Choi

et al. 2005

Biological & Pharmaceutical Bulletin

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“…Staurosporine reduced the tail current amplitude and slowed the decay kinetics, resulting in a crossover of the tail current. This phenomenon is evidence for open-state inhibition (39).…”

Section: Effects On Other Ion Channelsmentioning

confidence: 64%

Direct effect of protein kinase C inhibitors on cardiovascular ion channels

Son

Hong²,

Kim³

et al. 2011

BMB Reports

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“…Thus, the tail crossover phenomenon also suggests an interaction between fluvoxamine and the open state of Kv1.5, as previously reported. 16,[20][21][22][23] Inhibition was use-dependent, with effects enhanced at higher rates of channel activation. Usedependent inhibition is a feature of open channel blockers, because when channels open more frequently, blockers have a higher chance of binding to channel pores.…”

Section: Use-dependent Inhibition Of Kv15 By Fluvoxaminementioning

confidence: 99%

“…This value is similar to the d values of 0.16-0.19 obtained in previous experiments with open channel blockers of Kv1.5. 16,21,28,29) Although fluvoxamine is thought to be safer than other antidepressants such as TCA, [5][6][7][8][9] it has been reported to inhibit the HERG potassium channel 10) and may be related to ventricular arrhythmia.…”

Section: )mentioning

confidence: 99%

Inhibitory Action of Fluvoxamine on Kv1.5 Currents

Lee

Hahn

Choi

2010

Biological & Pharmaceutical Bulletin

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Fluvoxamine is a selective serotonin reuptake inhibitor that exerts antidepressant activity by inhibiting the reuptake of serotonin, or 5-hydroxytryptamine, in the central nervous system. Fluvoxamine shows negligible affinity for other neurotransmitter reuptake systems, [1][2][3][4] so it may have advantages over other antidepressants in the treatment of depression. For example, tricyclic antidepressant (TCA) is associated with an increased risk of cardiovascular events. [5][6][7][8][9] However, accumulating evidence suggests that fluvoxamine may increase cardiovascular risk through inhibition of the human ether-a-go-go related (HERG) potassium channel. 10)The drug may also be associated with ventricular arrhythmia.11) Pharmacological blockade of cardiac muscle voltage-gated K ϩ channels (Kv channels) is associated with adverse cardiac arrhythmias, suggesting that fluvoxamine may interact with cardiac Kv channels. However, the exact effects of fluvoxamine on cardiac Kv channels remain to be elucidated.Kv1.5 is a cardiovascular-specific Kv channel isoform. It has an important role in determining the length of cardiac action potentials, and is a target of antiarrhythmic drugs. 12)Kv1.5 is rapidly activated and is difficult to inactivate, so it contributes to the repolarization of atrial action potentials. Kv1.5 dysfunction results in prolonged cardiac action potentials, eventually leading to cardiac arrhythmias with serious morbidity. [13][14][15] In this study, we investigated whether fluvoxamine interacts with Kv1.5 cloned from rat brain and determined the mechanisms by which fluvoxamine acts on Kv1.5. MATERIALS AND METHODS Stable Transfection and Cell CultureChinese hamster ovary (CHO) cells expressing Kv1.5 channels from rat brain were used for electrophysiological recordings.16) Kv1.5 cDNA 17) was cloned into the plasmid expression vector pCR3.1 (Invitrogen Corp., San Diego, CA, U.S.A.). CHO cells were transfected with Kv1.5 cDNA using FuGENE6 reagent (Boehringer Mannheim, Indianapolis, IN, U.S.A.).Transfected cells were cultured in Iscove's modified Dulbecco's medium (Invitrogen Corp.) supplemented with 10% fetal bovine serum, 2 mM glutamine, 0.1 mM hypoxanthine, 0.01 mM thymidine, and 300 mg/ml G418 (A.G. Scientific, San Diego, CA, U.S.A.) in 95% humidified air-5% CO 2 at 37°C. Cultures were passaged every 4-5 d by brief trypsinethylenediaminetetraacetic acid treatment, seeded onto glass coverslips (diameter: 12 mm, Fisher Scientific, Pittsburgh, PA, U.S.A.) in a Petri dish, and used for electrophysiological recordings after 12-24 h.Electrophysiological Recordings Kv1.5 currents were recorded from CHO cells using a whole-cell patch-clamp technique 18) at room temperature (22-23°C). Micropipettes fabricated from glass capillary tubing (PG10165-4; World Precision Instruments, Sarasota, FL, U.S.A.) with a doublestage vertical puller (PC-10; Narishige, Tokyo) had a tip resistance of 2-3 MW when filled with pipette solution. Wholecell currents were amplified with a MultiClamp 700B amplifier (Molecular Devices, S...

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Class III Antiarrhythmic Effects of Zatebradine

Abstract: Background Zatebradine is a bradycardic agent that inhibits the hyperpolarization-activated current (I f ) in the rabbit

Cited by 84 publications

References 43 publications

Effects of Oxypeucedanin on hKv1.5 and Action Potential Duration

Effects of Oxypeucedanin on hKv1.5 and Action Potential Duration

Direct effect of protein kinase C inhibitors on cardiovascular ion channels

Inhibitory Action of Fluvoxamine on Kv1.5 Currents

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