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

Abstract

The different sodium channel currents (INa) were reported in myocardium, neuron, and skeletal muscles. To study whether INa is homogeneous within the heart, we applied whole-cell voltage clamp technique to evaluate fast voltage-gated INa in atrial and ventricular myocytes isolated from guinea pig heart. It was found that the density of inward INa was 50% greater at -35mV in atrial (-42.64 ± 2.9 pA/pF) than in ventricular (-27.5 ± 1.8 pA/pF, P < 0.01) myocytes. The half activation and inactivation voltages (V0.5) of INa in atrial myocytes were shifted 4.5 ± 0.2 and 9.6 ± 0.3 mV negative to those of ventricular myocytes. Time constants for INa activation (τm) and inactivation (τh) were twice as rapid in atrial as in ventricular myocytes. The τm and τh 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 INa from inactivation was slower in atrial than in ventricular myocytes, whereas the development of resting state inactivation was more rapid in atrial (τ = 67.5 ± 4.3 ms) than in ventricular (152.8 ± 7.5 ms, P < 0.01) myocytes. The results reveal marked heterogeneity of INa 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. © 2002 Elsevier Science Ltd. All rights reserved.