ikur - Dec 16 2009 Summary This chapter frambosa contains sections titled Introduction Molecular Biology of the Kv15 Channels IKur as a Therapeutic Target Organic Blockers of IKur Conclusions References IKur UltraRapid Delayed Rectifier Potassium Current A Therapeutic Target for Atrial Arrhythmias Novel Therapeutic Targets for Antiarrhythmic Drugs Wiley Online Aug 25 2017 I INTRODUCTION The voltagegated K channel alpha subunit K V 15 encoded by KCNA5 underlies the ultrarapid delayedrectifier K current I KurK V 15 is expressed in many organs including skeletal muscle brain and pulmonary arteries 324651 but it has drawn attention as an atrialselective pharmacological target against atrial fibrillation AF the most common cardiac Simulations were equilibrated for 300 beats at 1Hz pacing or 900 beats at 3Hz pacing After the 300 th or 900 th beat the time to 40 and 90 repolarization of the AP APD 40 and APD 90 were calculated along with diastolic intracellular Ca 2 concentration Ca 2 i CaT amp and time to 50 CaT decay Can inhibition of IKur promote atrial fibrillation Heart Pharmacological treatment with various antiarrhythmic agents for the termination or prevention of atrial fibrillation AF is not yet satisfactory This is in part because the drugs may not be sufficiently selective for the atrium and they often cause ventricular arrhythmias The ultrarapiddelayed Oct 11 2004 Background The ultrarapid outward current IKur is a major repolarizing current in human atrium and a potential target for treating atrial arrhythmias The effects of selective block of IKur by low concentrations of 4aminopyridine or the biphenyl derivative AVE 0118 were investigated on right atrial action potentials APs in trabeculae from patients in sinus rhythm SR or chronic atrial Inhibition of the voltagegated potassium channel Kv15 by Adrenergic modulation of ultrarapid delayed rectifier K Selective IKur Inhibitors for the Potential Treatment of Mar 4 2014 Role of IKur in controlling action potential shape and contractility in the human atrium influence of chronic atrial fibrillation Circulation 110 22992306 10116101CIR00001451556028871 Google Scholar Aug 8 2008 This study was designed to establish the pathologyspecific inhibitory effects of the IKur Ito IKACh blocker AVE0118 on atriumselective channels and its corresponding effects on action potential shape and effective refractory period in patients Oct 6 2024 Background Patients with atrial fibrillation AF exhibit a reduction in the ultrarapid outward potassium current IKur conducted by Kv15 channels Ion channels are modulated by regulatory subunits forming channelosomes One such regulatory family are leucinerich gliomainactivated proteins Lgi14 which interact with and modulate Kv1 in neurons However their impact in the heart Block of ultrarapid delayed rectified potassium current IKur present in atria but not in ventricles is thought to be a promising approach for atrialspecific therapy of atrial fibrillation AF However it has been shown that IKur block may abbreviate atrial repolarization and that lossoffunction mutations in KCNA5 which encodes Kv 15 channels responsible for IKur is associated with IKur UltraRapid Delayed Rectifier Potassium Current A Jan 6 2010 Cells exposed to antisense showed a highly significant approximately 50 reduction in IKur whether measured by step current at the end of a 400millisecond depolarizing pulse tail current at In Silico faja Assessment of Efficacy and Safety of IKur Block of ultrarapid delayed rectified potassium current IKur present in atria but not in ventricles is thought to be a promising approach for atrialspecific therapy of atrial fibrillation AF However it has been shown that IKur block may Cardiac Delayed Rectifier Potassium Channels in Health and May 9 2017 The ultrarapid delayed rectifier K current I Kur is often described as having slow and partial inactivation Fig 1 A shows normalized I Kur during a 1000 ms testpulse to 40 mV 5 ms after a 100ms pretest pulse to 40 mV to inactivate I to as recorded experimentally black 2 and from the original Courtemanche human atrial I Kur formulation blue Novel insights into IKur modulation by Lgi34 Implications Oct 19 2004 Background The ultrarapid outward current IKur is a major repolarizing current in human atrium and a potential target for treating atrial arrhythmias The effects of selective block of IKur by low concentrations of 4aminopyridine or the biphenyl derivative AVE 0118 were investigated on right atrial action potentials APs in trabeculae from patients in sinus rhythm SR or chronic atrial RateDependent Role of IKur in Human Atrial Repolarization Pathologyspecific effects of the IKurItoIKACh blocker Aug 25 2017 The KV15 potassium channel which underlies the ultrarapid delayedrectifier current IKur and is predominantly expressed in atria vs ventricles has emerge Revealing kinetics and statedependent binding properties of Effects of IKur blocker MK0448 on human right atrial action The ultrarapid delayed rectifier K current IKur in human atrial cells appears to correspond to Kv15 cloned channels and to play an important role in human atrial repolarization Kv15 channels have consensus sites for phosphorylation by protein kinase A and C suggesting possible modulation by a IKur UltraRapid Delayed Rectifier Potassium Current A Jun 19 2023 The voltagegated K channel plays a key role in atrial excitability conducting the ultrarapid rectifier K current IKur and contributing to the repolarization of the atrial action potential In silico study on the effects of IKur block kinetics on Role of IKur in Controlling Action Potential Shape and RateDependent Role of IKur in Human Atrial Repolarization Revealing kinetics and statedependent binding properties of Cardiac delayed rectifier potassium channels conduct outward potassium currents during the plateau phase of action potentials and play pivotal roles in cardiac repolarization These include IKs IKr and the atrial specific IKur channels In this May 5 2017 The atrialspecific ultrarapid delayed rectifier K current I Kur inactivates slowly but completely at depolarized voltagesThe consequences for I Kur ratedependence have not been analyzed in detail and currently available mathematical actionpotential AP models do not take into account experimentally observed I Kur inactivation dynamics Can inhibition of IKur promote atrial fibrillation PMC Role of IKur in controlling action potential shape and Apr 18 2017 We have recently disclosed 5phenylNpyridin2ylmethyl2pyrimidin5ylquinazolin4amine 1 as a potent IKur current blocker with selectivity versus hERG Na and Ca channels and an acceptable preclinical PK profile Upon further characterization in vivo compound 1 demonstrated an unacceptable level of brain penetration In an effort to reduce the level kahuku of brain penetration while
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