Serine/Threonine Phosphatases in Atrial Fibrillation

Jordi Heijman, Shokoufeh Ghezelbash, Xander H. T. Wehrens, Dobromir Dobrev*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

22 Citations (Web of Science)

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. (C) 2017 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)110-120
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume103
DOIs
Publication statusPublished - Feb 2017

Keywords

  • protein phosphatases
  • atrial fibrillation
  • ion channels
  • calcium handling
  • myofilaments
  • OUTWARD K+ CURRENT
  • CALCIUM-CHANNEL CA(V)1.2
  • HEART-FAILURE
  • PROTEIN PHOSPHATASES
  • MOLECULAR-MECHANISMS
  • DEPENDENT REGULATION
  • POTASSIUM CHANNEL
  • CARDIAC MYOCYTES
  • DOWN-REGULATION
  • ION CHANNELS

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