Fast Sodium Currents in Rat Atrial and Ventricular Myocytes

Activation of voltage-gated sodium channels (VGSC) underlies the generation and propagation of cardiac action potentials while their subsequent inactivation establishes a refractory period. Blockers of VGSC are highly effective as antiarrhythmic drugs in the treatment of atrial fibrillation. However, their use is limited because ventricular arrhythmias are a common side-effect. Atrial-ventricular differences in VGSC might be exploited to develop atrial-selective antiarrhythmic action. In this study, atrial-ventricular differences in the steady-state voltagedependent activation and inactivation of fast VGSC currents (INa)
were examined. INa was recorded from rat left atrial (n= 11) and left ventricular myocytes (n= 11) at room temperature using the whole-cell patch clamp technique. Recording solutions contained low equimolar sodium (5 mM) and Co2þ (1 mM) was used to block calcium currents. Voltage protocols had a holding potential of 120 mV. INa was recorded in response to a range of test pulses to investigate activation and at 30 mV following a range of conditioning pulses to investigate steadystateinactivation. Currents were normalized to whole-cell capacitance as an index of cell size and mean current-density voltage relations fitted by a modified Boltzmann relation. There was no significant difference between atrial and ventricular cells in current density-voltage relations: half-maximal voltages (V1/2) of activation were atrial, 47.851.5 mV, and ventricular, 46.851.1 mV. On the other hand, the V1/2 of inactivation for atrial and ventricular myocytes were 93.45 +/- 0.5 mV and 87.45 +/- 0.3 mV, respectively. Therefore, INa inactivation occurred at more negative voltages in rat atrial myocytes compared to ventricular myocytes.