title: 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).
abstract: Peri-operative atrial fibrillation (peri-op AF) is a common complication following thoracic surgery. This arrhythmia is thought to be triggered by an inflammatory response and can be reproduced in various animal models. Previous work has shown that the lipid inflammatory mediator, platelet-activating factor (PAF), synthesized by activated neutrophils, can induce atrial and ventricular arrhythmias as well as repolarization abnormalities in isolated ventricular myocytes. We have previously shown that carbamylated PAF-induced repolarization abnormalities result from the protein kinase C (PKC) ε-dependent phosphorylation of the two-pore domain potassium channel TASK-1. We now demonstrate that canine peri-op AF is associated with the phosphorylation-dependent loss of TASK-1 current. Further studies identified threonine 383 in the C terminus of human and canine TASK-1 as the phosphorylation site required for PAF-dependent inhibition of the channel. Using a novel phosphorylation site-specific antibody targeting the phosphorylated channel, we have determined that peri-op AF is associated with the loss of TASK-1 current and increased phosphorylation of TASK-1 at this site.
authors.affiliation: Department of Pharmacology, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Harleton
authors.forename: Alessandra
authors.initials: A
authors.lastname: Besana
authors.forename: George M
authors.initials: GM
authors.lastname: Comas
authors.forename: Peter
authors.initials: P
authors.lastname: Danilo
authors.forename: Tove S
authors.initials: TS
authors.lastname: Rosen
authors.forename: Michael
authors.initials: M
authors.lastname: Argenziano
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rosen
authors.forename: Richard B
authors.initials: RB
authors.lastname: Robinson
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Feinmark
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D004594:Electrophysiology; D006801:Humans; D007249:Inflammation; D008297:Male; D032342:Muscle Cells / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D059035:Perioperative Period; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation; D010972:Platelet Activating Factor / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D013912:Threonine / Q000737:chemistry
chemical_list: D009419:Nerve Tissue Proteins; D010972:Platelet Activating Factor; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; D013912:Threonine; D009195:Peroxidase; D011493:Protein Kinase C