On the mechanisms of arrhythmias in the myocardium of mXinα-deficient murine left atrial-pulmonary veins

LIFE SCIENCES

卷:83

Article

Lai, Yu-Jun^2,4  Huang, Eagle Yi-Kung³  Yeh, Hung-I⁴  Chen, Yen-Lin¹  Lin, Jim Jung-Ching⁵  Lin, Cheng-I^1,5 

[1] Natl Def Med Ctr, Inst Physiol, Dept Physiol & Biophys, Taipei 114, Taiwan

[2] Natl Def Med Ctr, Grad Inst Life Sci, Taipei 114, Taiwan

[3] Natl Def Med Ctr, Inst Pharmacol, Taipei 114, Taiwan

[4] Mackay Mem Hosp & Mackay Med, Dept Med Res, Nursing & Management Coll, Taipei, Taiwan

[5] Univ Iowa, Dept Biol Sci, Iowa City, IA USA

关键词: left atrial-pulmonary vein tissue;    murine Xin alpha gene-KO;    atrial fibrillation;    triggered and automatic rhythms;    fast pacing;    cardioactive agents;    multi-electrode mapping;    conduction velocity;    patch clamp;   

DOI  :  10.1016/j.lfs.2008.06.020

来源: Elsevier

【 摘 要 】

We have previously shown that left atrial-pulmonary vein tissue (LA-PV) can generate reentrant arrhythmias (atrial fibrillation, AF) in wild-type (mXin alpha+/+) but not in mXin alpha-null (mXin alpha-/-) mice. With the present experiments, we investigated the arrhythmogenic activity and the underlying mechanisms in mXin alpha+/+ vs. mXin alpha-/- LA-PV. Electrical activity and conduction velocity (CV) were recorded in LA-PV by means of a MED64 system. CV was significantly faster in mXin alpha+/+ than in mXin alpha-/- LA-PV and it was increased by 1 mu M isoproterenol (ISO). AF could be induced by fast pacing in the mXin alpha+/+ but not in mXin alpha-/- LA-PV where automatic rhythms could occur. ISO increased the incidence of AF in Xin alpha+/+ whereas it increased that of automatic rhythms in mXin alpha-/- LA-PV. In LA-PV with the right atrium attached (RA-LA-PV), automatic rhythms occurred in all preparations. In mXin alpha+/+ 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 mXin alpha-/- 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 mXin alpha-/- than mXin alpha+/+ LA-PV tissues. Whole-cell current clamp experiments also showed a less negative MDP in mXin alpha-/- vs. mXin alpha+/+ LA-PV cardiomyocytes. The fact that AF could be induced by fast pacing under several conditions in mXin alpha+/+ but not in mXin alpha-/- 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 mXin alpha-/- myocardial cells. In contrast, the non-impairment of automatic and triggered rhythms in mXin alpha-/- preparations may be due to the fact that the mechanisms underlying these rhythms do not involve cell-to-cell conduction. (C) 2008 Elsevier Inc. All rights reserved.

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