Heterogeneity of the properties of INa in epicardial and endocardial cells of rat ventricle.

1. Ventricular I(Na) heterogeneity was investigated in adult rat hearts. Differences in transient outward potassium current (Ito) were used to confirm isolation of subepicardial and subendocardial cells. Mean peak Ito was 6.0 +/- 0.7 and 1.6 +/- 0.45 pA/pF in epicardial and endocardial cells, respectively (P < < 0.01). 2. Maximum sodium conductance was smaller in subendocardial cells compared with subepicardial cells (2.39 +/- 0.11 vs 2.78 +/- 0.12 nS/pF, respectively; n=17 for both; 0.01 < P < 0.05) and 50% activation occurred at a slightly more negative potential (-47.6 +/- 0.8 vs -44.9 +/- 0.9 mV, respectively; n=10 for both; 0.01 < P < 0.05). 3. The potential for 50% inactivation was not significantly different in subepicardial compared with subendocardial cells (72.2 +/- 1.0 vs 72.8 +/- 2.2 mV, respectively; n=17 for both; NS). 4. Persistent sodium current density appeared smaller in subendocardial (n =19) compared with subepicardial (n=11) cells (at a test potential of -25 mV current, density was 0.118 +/- 0.041 vs 0.144 +/- 0.085 pA/pF, respectively), although this was not statistically significant due to large variability between cells. 5. Mathematical modelling of the cardiac action potential indicated that the combined effects of differences in current density and voltage dependence of sodium currents are unlikely to contribute to ventricular action potential heterogeneity between epicardial and endocardial cells.