Delayed Afterdepolarization and Triggered Activity, and the Effects of Antiarrhythmic Agents on these Abnormalities in the Atrioventricular Node and Ventricle

点击翻译按钮获取中文摘要

In order to elucidate the ionic mechanisms of delayed afterdepolarizations, action potential and voltage clamp studies were conducted in canine Purkinje fibers and rabbit atrioventricular node. A transient inward durrent, which was responisble for delayed afterdepolarizations, was obtained on repolarization from various test potentials to -40 - -60 mV under superfusions with 1 m acetylstrophantidin, 0.2 - 1 mM K^+, or 10 m. Ca^<2+> containing Tyrode's solutions, and inhibited by 0.1 mM Cd^<2+> (a Ca^<2+> channel blocker), 5 g/ml mexiletine (a Na^+ channel blocker), or 10 mM caffeine (a Ca^<2+> uptake blocker to sarcoplasmic reticulum). These results suggest that the transient inward current is mediated by a cyclic increase in intracellular Ca^<2+> concentration, and caused by a Ca^<2+> - induced activation of the nonspecific cation channel or a Ca^<2+> -induced activation of Na^+ -Ca^<2+> exchange system. To assess which mechanism is involved, Na^+ concentration in the Tyrode's solution was decreased to 50% of the control (replaced with either Li^+ or sucrose) since extracellular Na^+ does not affect the conductance of the nonspecific cation channel. A transient inward current induced by 0.5 mM K^+ tyrode's solution was then either decreased or inhibited by low Na^+. Next, the effect of 50 M La^<3+> Na^+ -Ca^<2+> exchange blocker) was studied on the transient inward current induced by 092 mM K^+ Tyrode in the presence of 1 mM Cd^<2+>. The transient inward current was again decreased or inhibited by La^<3+>. In conclusion, the results suggest that the transient inward current is induced by an activation of Na^+ -Ca^<2+> exchange system due to an increase in the intracellular Ca^<2+> concentration, and that a Ca^<2+> or a Na^+ channel blocker inhibits the transient inward current by suppressing the Na^+ -Ca^<2+> exchange system as these blockers reduce the intracellular Ca^<2+> or Na^+ overloading by inhibiting the transmembrane influxes of these ions, respectively.