Inhibitory Effect of a Late Sodium Current Blocker, NCC-3902, on the Automaticity of the Guinea Pig Pulmonary Vein Myocardium

Abstract

The effect of blocking the persistent component of the sodium channel current (late I Na ) on the automatic activity of the isolated guinea pig pulmonary vein myocardium was examined. NCC-3902 blocked late I Na , but did not affect other major ion channel currents stably expressed in cell lines. In isolated pulmonary vein cardiomyocytes, NCC-3902 blocked the late I Na induced by a ramp depolarizing voltage clamp pulse similar to that of the pacemaker depolarization observed in the pulmonary vein myocardium. In isolated pulmonary vein tissue, NCC-3902 decreased the frequency of automatic firing of the myocardium through a reduction of the pacemaker depolarization slope. In isolated pulmonary vein cardiomyocytes, NCC-3902 significantly reduced the firing frequency of Ca 2 transients, but had no effect on Ca 2 sparks. NCC-3902 affected neither the spontaneous beating rate of the right atrium nor the contractile force of the ventricular myocardium. Selective blockers of late I Na like NCC-3902, which inhibit the automatic activity of the pulmonary vein myocardium, appear to be promising as drugs for the pharmacological treatment of atrial fibrillation.

Negative Inotropic Effects of Class I Antiarrhythmics on Guinea Pig Ventricular Myocardium: Correlation with L-Type Ca²⁺ Channel Blockade

“…13) On the other hand, GS-458967 and NCC-3902, highly selective blockers of late I Na , were reported to decrease the contractile force of isolated myocardium only slightly. 4,14) It appears that selective blockade of late I Na causes only a weak negative inotropy.…”

Mechanisms for the α-Adrenoceptor-Mediated Positive Inotropy in Mouse Ventricular Myocardium: Enhancing Effect of Action Potential Prolongation

“…All experiments were approved by the Ethics Committee of Toho University Faculty of Pharmaceutical Sciences (22-41-507) and performed in accordance with the Guiding Principles for the Care and Use of Laboratory Animals approved by The Japanese Pharmacological Society. The basic experimental setup and procedures were the same as those in our previous studies [ 6 , 7 , 15 , 16 , 21 , 22 , 23 , 40 , 41 , 42 , 43 ].…”