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

Yu-Jun Lai, Eagle Yi-Kung Huang, Hung-I Yeh, Yen-Lin Chen, Jim Jung-Ching Lin, Cheng-I Lin

Index: Life Sci. 83(7-8) , 272-83, (2008)

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Abstract

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