Arrhythmias, elicited by catecholamines and serotonin, vanish in human chronic atrial fibrillation

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Torsten Christ - , University Hospital Hamburg Eppendorf (Author)
  • Nadiia Rozmaritsa - , Institute of Pharmacology and Toxicology (Author)
  • Andreas Engel - , Institute of Pharmacology and Toxicology (Author)
  • Emanuel Berk - , Institute of Pharmacology and Toxicology (Author)
  • Michael Knaut - , Department of Cardiac Surgery (at Dresden Heart Centre) (Author)
  • Katharina Metzner - , Institute of Pharmacology and Toxicology (Author)
  • Manuel Canteras - , University of Murcia (Author)
  • Ursula Ravens - , Institute of Pharmacology and Toxicology (Author)
  • Alberto Kaumann - , University Hospital Hamburg Eppendorf (Author)

Abstract

Atrial fibrillation (AF) is the most common heart rhythm disorder. Transient postoperative AF can be elicited by high sympathetic nervous system activity. Catecholamines and serotonin cause arrhythmias in atrial trabeculae from patients with sinus rhythm (SR), but whether these arrhythmias occur in patients with chronic AF is unknown. We compared the incidence of arrhythmic contractions caused by norepinephrine, epinephrine, serotonin, and forskolin in atrial trabeculae from patients with SR and patients with AF. In the patients with AF, arrhythmias were markedly reduced for the agonists and abolished for forskolin, whereas maximum inotropic responses were markedly blunted only for serotonin. Serotonin and forskolin produced spontaneous diastolic Ca(2+) releases in atrial myocytes from the patients with SR that were abolished or reduced in myocytes from the patients with AF. For matching L-type Ca(2+)-current (ICa,L) responses, serotonin required and produced ∼ 100-fold less cAMP/PKA at the Ca(2+) channel domain compared with the catecholamines and forskolin. Norepinephrine-evoked ICa,L responses were decreased by inhibition of Ca(2+)/calmodulin-dependent kinase II (CaMKII) in myocytes from patients with SR, but not in those from patients with AF. Agonist-evoked phosphorylation by CaMKII at phospholamban (Thr-17), but not of ryanodine2 (Ser-2814), was reduced in trabeculae from patients with AF. The decreased CaMKII activity may contribute to the blunting of agonist-evoked arrhythmias in the atrial myocardium of patients with AF.

Details

Original languageEnglish
Pages (from-to)11193-11198
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America : PNAS
Volume111
Issue number30
Publication statusPublished - 29 Jul 2014
Peer-reviewedYes

External IDs

Scopus 84905050495
researchoutputwizard legacy.publication#61463
researchoutputwizard legacy.publication#61628
PubMed 25024212
PubMedCentral PMC4121801
ORCID /0000-0003-3021-1338/work/142251877

Keywords

Keywords

  • Atrial Fibrillation/metabolism, Calcium/metabolism, Calcium Channels, L-Type/metabolism, Calcium-Binding Proteins/metabolism, Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism, Cardiotonic Agents/pharmacology, Catecholamines/pharmacology, Chronic Disease, Colforsin/pharmacology, Cyclic AMP/metabolism, Female, Heart Atria/metabolism, Humans, Male, Myocardial Contraction/drug effects, Phosphorylation/drug effects, Ryanodine/metabolism, Serotonin/pharmacology, Serotonin Receptor Agonists/pharmacology