Arrhythmias and spontaneous diastolic Ca(2+) releases elicited by catecholamines, serotonin, and forskolin were markedly reduced or abolished in atrial tissue from patients with chronic AF versus SR.
Does the incidence of arrhythmic contractions elicited by catecholamines and serotonin differ in atrial tissue from patients with chronic AF compared to those with sinus rhythm?
Arrhythmias elicited by catecholamines and serotonin are markedly reduced or abolished in atrial tissue from patients with chronic AF, potentially due to decreased CaMKII activity.
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.
Christ et al. (Mon,) conducted a other in Atrial fibrillation. Catecholamines, serotonin, and forskolin vs. Sinus rhythm tissue was evaluated on Incidence of arrhythmic contractions. Arrhythmias and spontaneous diastolic Ca(2+) releases elicited by catecholamines, serotonin, and forskolin were markedly reduced or abolished in atrial tissue from patients with chronic AF versus SR.