title: Serine/Threonine Phosphatases in Atrial Fibrillation.
abstract: Serine/threonine protein phosphatases control dephosphorylation of numerous cardiac proteins, including a variety of ion channels and calcium-handling proteins, thereby providing precise post-translational regulation of cardiac electrophysiology and function. Accordingly, dysfunction of this regulation can contribute to the initiation, maintenance and progression of cardiac arrhythmias. Atrial fibrillation (AF) is the most common heart rhythm disorder and is characterized by electrical, autonomic, calcium-handling, contractile, and structural remodeling, which include, among other things, changes in the phosphorylation status of a wide range of proteins. Here, we review AF-associated alterations in the phosphorylation of atrial ion channels, calcium-handling and contractile proteins, and their role in AF-pathophysiology. We highlight the mechanisms controlling the phosphorylation of these proteins and focus on the role of altered dephosphorylation via local type-1, type-2A and type-2B phosphatases (PP1, PP2A, and PP2B, also known as calcineurin, respectively). Finally, we discuss the challenges for phosphatase research, potential therapeutic significance of altered phosphatase-mediated protein dephosphorylation in AF, as well as future directions.
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute Maastricht, Faculty of Health, Medicine, and Life Sciences, Maastricht University, Maastricht, The Netherlands.
authors.forename: Jordi
authors.initials: J
authors.lastname: Heijman
authors.affiliation: Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Essen, Germany.
authors.forename: Shokoufeh
authors.initials: S
authors.lastname: Ghezelbash
authors.affiliation: Cardiovascular Research Institute, Department of Molecular Physiology and Biophysics, Department of Medicine (Cardiology), Pediatrics, Baylor College of Medicine, Houston, USA.
authors.forename: Xander H T
authors.initials: XH
authors.lastname: Wehrens
authors.affiliation: Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Essen, Germany. Electronic address: dobromir.dobrev@uk-essen.de.
authors.forename: Dobromir
authors.initials: D
authors.lastname: Dobrev
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D064752:Atrial Remodeling; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication; D004789:Enzyme Activation; D015870:Gene Expression; D006801:Humans; D058990:Molecular Targeted Therapy; D009200:Myocardial Contraction; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000244:Adenosine Diphosphate; D010749:Phosphoprotein Phosphatases; D002118:Calcium
keywords: atrial fibrillation; calcium handling; ion channels; myofilaments; protein phosphatases