A tetrodotoxin-sensitive persistent sodium current,IpNa, 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. Midmyocardial cells show a statistically significant (P<0.05) smallerIpNathan subendocardial and subepicardial myocytes. There was no significant difference inIpNacurrent density between subepicardial and subendocardial cells. Computer modeling studies support a role of this current in the dispersion of action potential duration across the ventricular wall.