Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction

OBJECTIVES: To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. METHODS: Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. RESULTS: Compared with HMI and control cardiomyocytes, significant prolongation of APD(50) or APD(90) (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (I(to)), the rapidly activated omponent of delayed rectifier potassium current (I(Kr)), the slowly activated component of delayed rectifier potassium current (I(Ks)), and the L-type calcium current (I(CaL)) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. CONCLUSIONS: Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca(2+) current are likely the underlying mechanism of action.