Phosphorylation of TASK-1 and its role in atrial arrhythmias
type: CreativeWork
description: Atrial fibrillation (AF) is the most common sustained arrhythmia in human patients, and is associated with an increased risk of stroke and other morbidity. Acute-onset AF is frequently associated with cardiothoracic surgery, and its initiation is thought to involve proinflammatory signaling. Activated neutrophils are known to be arrhythmogenic, and one of the inflammatory mediators released from neutrophils that contributes to arrhythmogenicity is the phospholipid platelet-activating factor (PAF). PAF acts via a G-protein coupled receptor, present in myocytes, to activate downstream signaling cascades. Data from our lab indicates that inhibition of the two-pore domain potassium channel TASK-1 may contribute to the arrhythmogenic effect of PAF. This study describes the identification of a novel phosphorylation site in the human TASK-1 carboxyl terminus, T383, and has explored the association between phosphorylation at this site and the development or maintenance of various models of atrial fibrillation. Signaling downstream of PAF was previously shown to inhibit the two pore-domain potassium channel TASK-1. This inhibition required the activity of the epsilon isoform of protein kinase C, and a putative phosphorylation site was identified in the murine TASK-1 channel. In this thesis, I have identified a homologous phosphorylation site in the human TASK-1 channel, T383, and have demonstrated that this site is targeted in native atrial myocardium. The known pro-inflammatory effects of PAF, as well as the action potential abnormalities observed in previous studies after direct TASK-1 antagonism in isolated mouse ventricular myocytes, suggested that inhibitory phosphorylation at T383 could play a role in arrhythmias, particularly those with an inflammatory component to their etiology. Therefore, an aim of this thesis was to investigate the relationship between inhibitory TASK-1 phosphorylation and peri-operative atrial fibrillation (POAF) in a canine model. POAF is an acu…
abstract: Atrial fibrillation (AF) is the most common sustained arrhythmia in human patients, and is associated with an increased risk of stroke and other morbidity. Acute-onset AF is frequently associated with cardiothoracic surgery, and its initiation is thought to involve proinflammatory signaling. Activated neutrophils are known to be arrhythmogenic, and one of the inflammatory mediators released from neutrophils that contributes to arrhythmogenicity is the phospholipid platelet-activating factor (PAF). PAF acts via a G-protein coupled receptor, present in myocytes, to activate downstream signaling cascades. Data from our lab indicates that inhibition of the two-pore domain potassium channel TASK-1 may contribute to the arrhythmogenic effect of PAF. This study describes the identification of a novel phosphorylation site in the human TASK-1 carboxyl terminus, T383, and has explored the association between phosphorylation at this site and the development or maintenance of various models of atrial fibrillation. Signaling downstream of PAF was previously shown to inhibit the two pore-domain potassium channel TASK-1. This inhibition required the activity of the epsilon isoform of protein kinase C, and a putative phosphorylation site was identified in the murine TASK-1 channel. In this thesis, I have identified a homologous phosphorylation site in the human TASK-1 channel, T383, and have demonstrated that this site is targeted in native atrial myocardium. The known pro-inflammatory effects of PAF, as well as the action potential abnormalities observed in previous studies after direct TASK-1 antagonism in isolated mouse ventricular myocytes, suggested that inhibitory phosphorylation at T383 could play a role in arrhythmias, particularly those with an inflammatory component to their etiology. Therefore, an aim of this thesis was to investigate the relationship between inhibitory TASK-1 phosphorylation and peri-operative atrial fibrillation (POAF) in a canine model. POAF is an acu…
author: Harleton, Erin Rachel
language: English
keywords: Pharmacology, Atrial fibrillation, Phosphorylation, Potassium channels, Physiology, Biology
date published: 2011
date modified: 2026-07-24T01:44:16Z
provider: Columbia University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Columbia University

PropertyValue
property ID: DOI
value: 10.7916/D8GT5V4P