Heterogeneity of sodium current in atrial vs epicardial ventricular myocytes of adult guinea pig hearts

The different sodium channel currents (I(Na)) were reported in myocardium, neuron, and skeletal muscles. To study whether I(Na) is homogeneous within the heart, we applied whole-cell voltage clamp technique to evaluate fast voltage-gated I(Na) in atrial and ventricular myocytes isolated from guinea pig heart. It was found that the density of inward I(Na) was 50% greater at -35 mV in atrial (-42.6+/-2.9 pA/pF) than in ventricular (-27.5+/-1.8 pA/pF, P<0.01) myocytes. The half activation and inactivation voltages (V(0.5)) of I(Na) in atrial myocytes were shifted 4.5+/-0.2 and 9.6+/-0.3 mV negative to those of ventricular myocytes. Time constants for I(Na) activation (tau(m)) and inactivation (tau(h)) were twice as rapid in atrial as in ventricular myocytes. The tau(m) and tau(h) were 0.34+/-0.03 and 1.36+/-0.07 ms for atrial myocytes, and 0.69+/-0.05 and 3.27+/-0.23 ms for ventricular myocytes, respectively. Recovery of I(Na) from inactivation was slower in atrial than in ventricular myocytes, whereas the development of resting state inactivation was more rapid in atrial (tau=67.5+/-4.3 ms) than in ventricular (152.8+/-7.5 ms, P<0.01) myocytes. The results reveal marked heterogeneity of I(Na) in the density and biophysical properties in atrial and ventricular myocytes, and the study suggests the potential possibility of tissue specific cardiac sodium channel isoforms.