Late post-myocardial infarction induces a tetrodotoxin-resistant Na+ current in rat cardiomyocytes

Left ventricular remodeling after myocardial infarction is accompanied by e lectrical abnormalities that might predispose to rhythm disturbances. To ge t insight into the ionic mechanisms involved, we studied myocytes isolated from four different regions of the rat ventricles, 4-6 months after ligatio n of the left coronary artery. Using the whole-cell patch-clamp technique, we never observed T-type Ca2+ current in both diseased and control hearts, In contrast, in 41 out of 78 cells isolated from 16 post-myocardial infarct ed rats, analysed in the presence of 30 mM Na+ ions, we found a tetrodotoxi n (TTX)-resistant Na+ current with quite variable amplitude in every invest igated region, Albeit being resistant to 100 mu M TTX, this Na+-dependent c urrent was highly sensitive to lidocaine since 3 mu M lidocaine induced abo ut 65% tonic block. It was also inhibited by 5 mu M nifedipine and 2 mM Co2 +, but was insensitive to 100 mu M Ni2+. The TTX-resistant Na+ channel avai lability was shifted rightward by 25-30mV with respect to TTS-sensitive Na current; therefore, a large "window current" might flow in the voltage ran ge from -70 to -20 mV. In conclusion, in late post-myocardial infarction, a Na+ current with specific kinetics and pharmacology may provide inward cha rges in a critical range of membrane voltages that are able to alter action potential time course and trigger ventricular arrhythmia, These apparent n ew characteristics of the Na+ channel might result in part from environment al changes during heart remodeling. (C) 2000 Academic Press.