title: On the mechanisms of arrhythmias in the myocardium of mXinalpha-deficient murine left atrial-pulmonary veins.
abstract: We have previously shown that left atrial-pulmonary vein tissue (LA-PV) can generate reentrant arrhythmias (atrial fibrillation, AF) in wild-type (mXinalpha+/+) but not in mXinalpha-null (mXinalpha-/-) mice. With the present experiments, we investigated the arrhythmogenic activity and the underlying mechanisms in mXinalpha+/+ vs. mXinalpha-/- LA-PV. Electrical activity and conduction velocity (CV) were recorded in LA-PV by means of a MED64 system. CV was significantly faster in mXinalpha+/+ than in mXinalpha-/- LA-PV and it was increased by 1 muM isoproterenol (ISO). AF could be induced by fast pacing in the mXinalpha+/+ but not in mXinalpha-/- LA-PV where automatic rhythms could occur. ISO increased the incidence of AF in Xinalpha+/+ whereas it increased that of automatic rhythms in mXinalpha-/- LA-PV. In LA-PV with the right atrium attached (RA-LA-PV), automatic rhythms occurred in all preparations. In mXinalpha+/+ RA-LA-PV simultaneously treated with ISO, strophanthidin and atropine, the incidence of the automatic rhythm was about the same, but AF increased significantly. In contrast, in mXinalpha-/- RA-LA-PV under the same condition, the automatic rhythm was markedly enhanced, but still no AF occurred. Conventional microelectrode techniques showed a longer APD(90) and a less negative maximum diastolic potential (MDP) in mXinalpha-/- than mXinalpha+/+ LA-PV tissues. Whole-cell current clamp experiments also showed a less negative MDP in mXinalpha-/- vs. mXinalpha+/+ LA-PV cardiomyocytes. The fact that AF could be induced by fast pacing under several conditions in mXinalpha+/+ but not in mXinalpha-/- LA-PV preparations appears to be due to a slower CV, a prolonged APD(90), a less negative MDP and possibly larger areas of conduction block in mXinalpha-/- myocardial cells. In contrast, the non-impairment of automatic and triggered rhythms in mXinalpha-/- preparations may be due to the fact that the mechanisms underlying these rhythms do not involve cell-to-cell conduction.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yu-Jun
authors.initials: YJ
authors.lastname: Lai
authors.forename: Eagle Yi-Kung
authors.initials: EY
authors.lastname: Huang
authors.forename: Hung-I
authors.initials: HI
authors.lastname: Yeh
authors.forename: Yen-Lin
authors.initials: YL
authors.lastname: Chen
authors.forename: Jim Jung-Ching
authors.initials: JJ
authors.lastname: Lin
authors.forename: Cheng-I
authors.initials: CI
authors.lastname: Lin
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000235:genetics / Q000503:physiopathology*; D001285:Atropine / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004553:Electric Conductivity; D022062:Electrophysiologic Techniques, Cardiac / Q000379:methods; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium; D009687:Nuclear Proteins / Q000235:genetics; D011667:Pulmonary Veins / Q000503:physiopathology*; D013327:Strophanthidin / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C118478:Xin protein, mouse; D013327:Strophanthidin; D001285:Atropine; D007545:Isoproterenol