title: Effect of vagal stimulation and differential densities of M2 receptor and IK,ACh in canine atria.
abstract: OBJECTIVE
  We investigated the electrophysiological effect of vagal stimulation (VS) on atrial myocardium in vivo and differential densities of M(2) receptor and acetylcholine-induced inward rectifier K(+) current (I(K,ACh)) to discuss the mechanisms of atrial fibrillation (AF).
  
  
  METHODS
  With the monophasic action potential (MAP) recording technique, data from twenty-four sites, i.e. right atrial appendage (RAA), left atrial appendage (LAA), right atrium (RA) and left atrium (LA) were recorded by electrode probes, which were applied to the epicardial atrial surface of each dog. After cervical vagosympathetic cut, VS(1) (20 Hz, 0.2 ms pulse duration and at a voltage 10 V), VS(2) (20 Hz, 0.2 ms pulse duration and at a voltage 30 V) and sinus node (SN) damage were administrated respectively. MAP, dispersion of action potential duration (dAPD) and AF was recorded. Then, RAA, LAA, RA and LA were dissected. Finally, distribution of M(2) receptors and I(K,ACh) in atrial myocardium were measured by western blot and patch clamp respectively.
  
  
  RESULTS
  During VS(1) and VS(2), AF could be induced at first in right atrial appendage (RAA) and right atrium (RA) without left atrial appendage (LAA) and left atrium (LA). Compared to the parameters in control group and VS(2) group, dAPD was increased significantly by VS(1) and SN damage, but there was no significant difference between control group and VS(2) group. However, AF was not evoked after SN damage. Densities of M(2) receptor and I(K,ACh) were higher in RAA, LAA than those in LA and RA (M(2) receptor: 1 and 1.01 over 0.83 and 0.51, P<0.05; I(K,ACh): 20+/-0.89, 19+/-0.82, 14+/-0.64, 9+/-0.45 pA/pF, P<0.05). Furthermore, densities of M(2) receptor and I(K,ACh) were higher in LA than those in RA (P<0.05).
  
  
  CONCLUSIONS
  Decreased APD is the base in initiation of cholinergic AF by VS and increased dAPD alone can not induce AF. A greater abundance of M(2) receptor and I(KACh) in RAA and LAA imply atrial appendage plays an important role in initiation of cholinergic AF.
authors.affiliation: Department of Cardiology, Renmin Hospital, Wuhan University School of Medicine, JieFang Road 238, Wuhan 430060, PR China.
authors.forename: Qing-Yan
authors.initials: QY
authors.lastname: Zhao
authors.forename: Cong-Xin
authors.initials: CX
authors.lastname: Huang
authors.forename: Jin-Jun
authors.initials: JJ
authors.lastname: Liang
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Geng-Shan
authors.initials: GS
authors.lastname: Li
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D020517:Atrial Appendage / Q000294:innervation; D001281:Atrial Fibrillation / Q000209:etiology / Q000503:physiopathology*; D016279:Atrial Function, Left / Q000502:physiology; D016280:Atrial Function, Right / Q000502:physiology; D015153:Blotting, Western; D004195:Disease Models, Animal; D004285:Dogs; D004558:Electric Stimulation; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology*; D011336:Probability; D011897:Random Allocation; D043585:Receptor, Muscarinic M2 / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity; D014630:Vagus Nerve
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D043585:Receptor, Muscarinic M2; D000109:Acetylcholine