Serine/Threonine Phosphatases in Atrial Fibrillation. (February 2017)

• Record Type: Journal Article
• Authors: Heijman, Jordi; Ghezelbash, Shokoufeh; Wehrens, Xander H.T.; Dobrev, Dobromir
• Is Part Of: Journal of molecular and cellular cardiology. Volume 103(2017)
• Page Start: 110
• Page End: 120
• Publication Date: 2017-02
• Subjects: AF atrial fibrillation -- AP action potential -- β-AR β-adrenoceptor -- cAF chronic AF -- CaMKII Ca2+/calmodulin-dependent protein kinase type-II -- cMyBP-C cardiac myosin-binding protein-C -- Cn calcineurin -- DAD delayed afterdepolarization -- HF heart failure -- ICa, L L-type Ca2+-current -- IK1 basal inward-rectifier K+-current -- IK2P two-pore domain K+-current -- IK, ACh acetylcholine-dependent inward-rectifier K+-current -- IKr rapid delayed-rectifier K+-current -- IKs slow delayed-rectifier K+-current -- IKur ultra-rapid delayed-rectifier K+-current -- INa Na+-current -- Ito transient-outward K+-current -- NCX1 Na+-Ca2+-exchanger type-1 -- pAF paroxysmal AF -- PKA protein kinase-A -- PKC protein kinase-C -- PLB phospholamban -- PP1 protein phosphatase type-1 -- PP2A protein phosphatase type-2A -- RyR2 ryanodine receptor type-2 -- SERCA2a sarcoplasmic reticulum Ca2+-ATPase type-2a -- SR sarcoplasmic reticulum -- TnI troponin-I; protein phosphatases -- atrial fibrillation -- ion channels -- calcium handling -- myofilaments; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2016.12.009
• Languages: English
• ISSNs: 0022-2828

Abstract

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. Highlights: Atrial fibrillation (AF) is associated with profound atrial remodeling Global cardiomyocyte PP1, PP2A and calcineurin activities are increased in AF patients PP1, PP2A and calcineurin are involved in proarrhythmic atrial remodeling Methodological challenges exist to elucidate the precise roles of phosphatases in AF Phosphatases represent a potential therapeutic target for AF