Document Detail

Cholinergic atrial fibrillation: I(K,ACh) gradients determine unequal left/right atrial frequencies and rotor dynamics.
MedLine Citation:
PMID:  14553826     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: We tested the hypothesis that left atrial (LA) myocytes are more sensitive to acetylcholine (ACh) than right atrial (RA) myocytes, which results in a greater dose-dependent increase in LA than RA rotor frequency, increased LA-to-RA frequency gradient and increased incidence of wavelet formation during atrial fibrillation (AF). METHODS AND RESULTS: AF was induced in seven Langendorff-perfused sheep hearts in the presence of ACh (0.1-4.0 microM) and studied using optical mapping and bipolar recordings. Dominant frequencies (DFs) were determined in optical and electrical signals and phase movies were used to identify rotors and quantify their dynamics. DFs in both atria increased monotonically with ACh concentration until saturation, but the LA frequency predominated at all concentrations. Rotors were also seen more often in the LA, and although their life span decreased, their frequency and number of rotations increased. Patch-clamp studies demonstrated that ACh-activated potassium current (I(K,ACh)) density was greater in LA than RA sheep myocytes. Additionally, ribonuclease protection assay demonstrated that Kir3.4 and Kir3.1 mRNAs were more abundant in LA than in RA. CONCLUSIONS: A greater abundance of Kir3.x channels and higher I(K,ACh) density in LA than RA myocytes result in greater ACh-induced speeding-up of rotors in the LA than in the RA, which explains the ACh dose-dependent changes in overall AF frequency and wavelet formation.
Farzad Sarmast; Arun Kolli; Alexey Zaitsev; Keely Parisian; Amit S Dhamoon; Prabal K Guha; Mark Warren; Justus M B Anumonwo; Steven M Taffet; Omer Berenfeld; José Jalife
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cardiovascular research     Volume:  59     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-10-13     Completed Date:  2004-04-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  863-73     Citation Subset:  IM    
Institute for Cardiovascular Research and Department of Pharmacology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.
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MeSH Terms
Acetylcholine / pharmacology*
Action Potentials / drug effects
Atrial Fibrillation / physiopathology*
Dose-Response Relationship, Drug
Heart Atria
Myocytes, Cardiac / drug effects*
Potassium Channels / drug effects
Signal Processing, Computer-Assisted
Grant Support
Reg. No./Substance:
0/Potassium Channels; 51-84-3/Acetylcholine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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