Ability to Induce Atrial Fibrillation in the Peri-operative Period Is Associated with Phosphorylation-dependent Inhibition of TWIK Protein-related Acid-sensitive Potassium Channel 1 (TASK-1)

Harleton, Erin; Besana, Alessandra; Comas, George M.; Danilo, Peter; Rosen, Tove S.; Argenziano, Michael; Rosen, Michael R.; Robinson, Richard B.; Feinmark, Steven J.

doi:10.1074/jbc.m112.404095

Cited by 22 publications

(15 citation statements)

References 36 publications

(45 reference statements)

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“…The same group recently reported an association between K 2P 3.1 inhibition with atrial fibrillation in a canine model of peri-operative AF (113). However, the study did not irrevocably show whether K 2P 3.1 inhibition contributed to arrhythmogenesis or whether it was secondary to AF induction in this specific animal model (173).…”

Section: Cardiac Potassium Channels and Arrhythmiamentioning

confidence: 67%

Cardiac Potassium Channel Subtypes: New Roles in Repolarization and Arrhythmia

Schmitt

Grunnet

Olesen

2014

Physiological Reviews

196

197

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About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K+ channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K+ channels drive the late repolarization of the ventricle with some redundancy, and in atria this repolarization reserve is supplemented by the fairly atrial-specific KV1.5, Kir3, KCa, and K2P channels. The role of the latter two subtypes in atria is currently being clarified, and several findings indicate that they could constitute targets for new pharmacological treatment of atrial fibrillation. The interplay between the different K+ channel subtypes in both atria and ventricle is dynamic, and a significant up- and downregulation occurs in disease states such as atrial fibrillation or heart failure. The underlying posttranscriptional and posttranslational remodeling of the individual K+ channels changes their activity and significance relative to each other, and they must be viewed together to understand their role in keeping a stable heart rhythm, also under menacing conditions like attacks of reentry arrhythmia.

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Section: Cardiac Potassium Channels and Arrhythmiamentioning

confidence: 67%

Cardiac Potassium Channel Subtypes: New Roles in Repolarization and Arrhythmia

Schmitt

Grunnet

Olesen

2014

Physiological Reviews

196

197

View full text Add to dashboard Cite

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“…The SR and cAF versions of the Grandi et al 36 computational model of the human atrial cardiomyocyte, including our recent update with Na + -dependent regulation of I K1 and I K,ACh , 37 was extended with a formulation for the K 2P 3.1 current (Supplemental Methods, Table II, and Figure I in the online-only Data Supplement).…”

Section: Computational Modelingmentioning

confidence: 99%

Upregulation of K _2P 3.1 K ⁺ Current Causes Action Potential Shortening in Patients With Chronic Atrial Fibrillation

et al. 2015

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Background-Antiarrhythmic management of atrial fibrillation (AF) remains a major clinical challenge. Mechanismbased approaches to AF therapy are sought to increase effectiveness and to provide individualized patient care. K 2P 3.1 (TASK-1 [tandem of P domains in a weak inward-rectifying K + channel-related acid-sensitive K + channel-1]) 2-poredomain K + (K 2P ) channels have been implicated in action potential regulation in animal models. However, their role in the pathophysiology and treatment of paroxysmal and chronic patients with AF is unknown. Methods and Results-Right and left atrial tissue was obtained from patients with paroxysmal or chronic AF and from control subjects in sinus rhythm. Ion channel expression was analyzed by quantitative real-time polymerase chain reaction and Western blot. Membrane currents and action potentials were recorded using voltage-and current-clamp techniques. K 2P 3.1 subunits exhibited predominantly atrial expression, and atrial K 2P 3.1 transcript levels were highest among functional K 2P channels. K 2P 3.1 mRNA and protein levels were increased in chronic AF. Enhancement of corresponding currents in the right atrium resulted in shortened action potential duration at 90% of repolarization (APD 90 ) compared with patients in sinus rhythm. In contrast, K 2P 3.1 expression was not significantly affected in subjects with paroxysmal AF. Pharmacological K 2P 3.1 inhibition prolonged APD 90 in atrial myocytes from patients with chronic AF to values observed among control subjects in sinus rhythm. Conclusions-Enhancement of atrium-selective K 2P 3.1 currents contributes to APD shortening in patients with chronic AF, and K 2P 3.1 channel inhibition reverses AF-related APD shortening. These results highlight the potential of K 2P 3.1 as a novel drug target for mechanism-based AF therapy.

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“…Another cytokine, IL-8, can exacerbate cardiac injury by enhancing leukocyte activation and accumulation: neutrophils activation alone may be arrhythmogenic because activated neutrophils bind to cardiac myocytes causing changes in myocyte electrical activity with delayed repolarization, early afterdepolarizations, and arrest of repolarization [ 51 ]. Furthermore one of the neutrophil products that contributes to arrhythmogenicity is the inflammatory lipid mediator, platelet-activating factor that may induce AF in perioperative period, reducing potassium current and favoring early afterdepolarizations occurrence [ 52 ]. Toll-like receptors also seem to be involved in atrial remodeling in postoperative AF [ 51 ]; in particular, toll-like receptor 4 activation decreases transient outward potassium current (I to ), which increases action potential duration [ 53 ].…”

Section: Pathogenesismentioning

confidence: 99%

Ischemic Stroke after Heart Transplantation

et al. 2016

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Cerebrovascular complications after orthotopic heart transplantation (OHT) are more common in comparison with neurological sequelae subsequent to routine cardiac surgery. Ischemic stroke and transient ischemic attack (TIA) are more common (with an incidence of up to 13%) than intracranial hemorrhage (2.5%). Clinically, ischemic stroke is manifested by the appearance of focal neurologic deficits, although sometimes a stroke may be silent or manifests itself by the appearance of encephalopathy, reflecting a diffuse brain disorder. Ischemic stroke subtypes distribution in perioperative and postoperative period after OHT is very different from classical distribution, with different pathogenic mechanisms. Infact, ischemic stroke may be caused by less common and unusual mechanisms, linked to surgical procedures and to postoperative inflammation, peculiar to this group of patients. However, many strokes (40%) occur without a well-defined etiology (cryptogenic strokes). A silent atrial fibrillation (AF) may play a role in pathogenesis of these strokes and P wave dispersion may represent a predictor of AF. In OHT patients, P wave dispersion correlates with homocysteine plasma levels and hyperhomocysteinemia could play a role in the pathogenesis of these strokes with multiple mechanisms increasing the risk of AF. In conclusion, stroke after heart transplantation represents a complication with considerable impact not only on mortality but also on subsequent poor functional outcome.

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Ability to Induce Atrial Fibrillation in the Peri-operative Period Is Associated with Phosphorylation-dependent Inhibition of TWIK Protein-related Acid-sensitive Potassium Channel 1 (TASK-1)

Cited by 22 publications

References 36 publications

Cardiac Potassium Channel Subtypes: New Roles in Repolarization and Arrhythmia

Cardiac Potassium Channel Subtypes: New Roles in Repolarization and Arrhythmia

Upregulation of K _2P 3.1 K ⁺ Current Causes Action Potential Shortening in Patients With Chronic Atrial Fibrillation

Ischemic Stroke after Heart Transplantation

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Ability to Induce Atrial Fibrillation in the Peri-operative Period Is Associated with Phosphorylation-dependent Inhibition of TWIK Protein-related Acid-sensitive Potassium Channel 1 (TASK-1)

Cited by 22 publications

References 36 publications

Cardiac Potassium Channel Subtypes: New Roles in Repolarization and Arrhythmia

Cardiac Potassium Channel Subtypes: New Roles in Repolarization and Arrhythmia

Upregulation of K 2P 3.1 K + Current Causes Action Potential Shortening in Patients With Chronic Atrial Fibrillation

Ischemic Stroke after Heart Transplantation

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Upregulation of K _2P 3.1 K ⁺ Current Causes Action Potential Shortening in Patients With Chronic Atrial Fibrillation