Arrhythmias, elicited by catecholamines and serotonin, vanish in human chronic atrial fibrillation
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Arrhythmias, elicited by catecholamines and serotonin, vanish in human chronic atrial fibrillation. / Christ, Torsten; Rozmaritsa, Nadiia; Engel, Andreas; Berk, Emanuel; Knaut, Michael; Metzner, Katharina; Canteras, Manuel; Ravens, Ursula; Kaumann, Alberto .
In: P NATL ACAD SCI USA, Vol. 111, No. 30, 29.07.2014, p. 11193-8.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Arrhythmias, elicited by catecholamines and serotonin, vanish in human chronic atrial fibrillation
AU - Christ, Torsten
AU - Rozmaritsa, Nadiia
AU - Engel, Andreas
AU - Berk, Emanuel
AU - Knaut, Michael
AU - Metzner, Katharina
AU - Canteras, Manuel
AU - Ravens, Ursula
AU - Kaumann, Alberto
PY - 2014/7/29
Y1 - 2014/7/29
N2 - 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.
AB - 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.
KW - Atrial Fibrillation
KW - Calcium
KW - Calcium Channels, L-Type
KW - Calcium-Binding Proteins
KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2
KW - Cardiotonic Agents
KW - Catecholamines
KW - Chronic Disease
KW - Colforsin
KW - Cyclic AMP
KW - Female
KW - Heart Atria
KW - Humans
KW - Male
KW - Myocardial Contraction
KW - Phosphorylation
KW - Ryanodine
KW - Serotonin
KW - Serotonin Receptor Agonists
U2 - 10.1073/pnas.1324132111
DO - 10.1073/pnas.1324132111
M3 - SCORING: Journal article
C2 - 25024212
VL - 111
SP - 11193
EP - 11198
JO - P NATL ACAD SCI USA
JF - P NATL ACAD SCI USA
SN - 0027-8424
IS - 30
ER -