title: Arrhythmias, elicited by catecholamines and serotonin, vanish in human chronic atrial fibrillation.
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.
authors.affiliation: Departments of Pharmacology and Toxicology and t.christ@uke.de kaumann@um.es.
authors.forename: Torsten
authors.initials: T
authors.lastname: Christ
authors.affiliation: Departments of Pharmacology and Toxicology and.
authors.forename: Nadiia
authors.initials: N
authors.lastname: Rozmaritsa
authors.affiliation: Departments of Pharmacology and Toxicology and.
authors.forename: Andreas
authors.initials: A
authors.lastname: Engel
authors.affiliation: Departments of Pharmacology and Toxicology and.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Berk
authors.affiliation: Heart Surgery, Dresden University of Technology, 01307 Dresden, Germany; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Knaut
authors.affiliation: Departments of Pharmacology and Toxicology and.
authors.forename: Katharina
authors.initials: K
authors.lastname: Metzner
authors.affiliation: Departments of Biostatistics and.
authors.forename: Manuel
authors.initials: M
authors.lastname: Canteras
authors.affiliation: Departments of Pharmacology and Toxicology and.
authors.forename: Ursula
authors.initials: U
authors.lastname: Ravens
authors.affiliation: Pharmacology, University of Murcia, 30100 Murcia, Spain t.christ@uke.de kaumann@um.es.
authors.forename: Alberto
authors.initials: A
authors.lastname: Kaumann
mesh_terms: D001281:Atrial Fibrillation / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology*; D002908:Chronic Disease; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D012433:Ryanodine / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D000099211:Phospholamban
chemical_list: D002118:Calcium; D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002316:Cardiotonic Agents; D002395:Catecholamines; D005576:Colforsin; D000242:Cyclic AMP; D012433:Ryanodine; D012701:Serotonin; D017366:Serotonin Receptor Agonists; D000099211:Phospholamban