Tonic block of the Na+ current in single atrial and ventricular guineapig myocytes, by a new antiarrhythmic drug, Ro 22-9194

Ro 22-9194 reduced the Na + current in the atrial myocytes as well as ventricular myocytes in a tonic block fashion. Ro 22-9194 had a higher affinity to the inactivated state Na + channels (Kd 1 = 3.3 μM in atrial myocytes, Kd 1 = 10.3 μM in ventricular myocytes) than to those in the rested state (Kd R = 91 μM in atrial myocytes, Kd R = 180 μM in ventricular myocytes), which indicated that Ro 22-9194 had a higher affinity to the Na + channels in atrial myocytes than in ventricular myocytes. Ro 22-9194 shifted the inactivation curve in the hyperpolarized direction in both atrial and ventricular myocytes. These findings suggest that Ro 22-9194 more strongly inhibited the Na + channel of the atrial myocytes of the diseased hearts with the depolarized membranes potentials than the Na + channels in ventricular myocytes.