Abstract-A tetrodotoxin-sensitive persistent sodium current, I pNa , was found in guinea pig ventricular myocytes by whole-cell patch clamping. This current was characterized in cells derived from the basal left ventricular subendocardium, midmyocardium, and subepicardium. Key Words: persistent sodium current Ⅲ guinea pig ventricle Ⅲ regional differences F irst indications for a slowly inactivating, persistent sodium current in cardiac cells came from studies on Purkinje fibers of dogs and rabbits.1,2 This was followed by the discovery of slowly inactivating sodium channels in ventricular myocytes of rats. Subsequently, a small late sodium current was described in guinea pig ventricular myocytes using single-channel and whole-cell patch clamping. 4 This study also suggested a significant effect of the late sodium current on action potential duration in ventricular cells: application of 60 mol/L tetrodotoxin (TTX) reversibly shortened action potential duration at 95% repolarization (ADP 95 ) by about 10%. Kiyosue et al 4 speculated that this was because of block of slowly inactivating sodium channels.Additional studies investigated the changes in the I-V relation of a slowly inactivating, TTX-sensitive sodium current (I pNa ) in rat ventricular myocytes in the absence and presence of hypoxia. 5,6 This persistent sodium current increased during hypoxia, and, thus, it was suggested that it could be involved in the development of early after depolarizations (EADs) and arrhythmias during hypoxic states. Most recently, Maltsev et al 7 showed that a persistent sodium current (which they called the late sodium current) is present in ventricular myocytes from human midmyocardium in normal donor hearts and heart failure patients. Interestingly, they found a similar (15% to 20%) reduction in action potential duration (APD) after application of 1.5 mol/L TTX, as previously described 4 in guinea pigs. They also showed that TTX abolished EADs in myocytes isolated from heart failure patients. Computer modeling studies fit these data surprisingly well. It has been demonstrated 8 that EADs can be induced in a cell model by increasing I pNa ; this mechanism also requires that the inactivation curve of the fast sodium current is shifted in the depolarizing direction, as has been observed in an SCN5A missense mutation. 9 An increase in late sodium current is also present in some well-known genetic predispositions to arrhythmias, for example, one type of the long-QT syndrome.