Transmembrane action potential heterogeneity in the canine isolated arterially perfused right atrium: effect of IKr and IKur/Ito block

The role of electrical heterogeneity in development of cardiac arrhythmias is well recognized. The extent to which transmembrane action potential (TAP) heterogeneity contributes to the normal electrophysiology of well-oxygenated atria is not well defined. The principal objective of the present study was to define regional and transmural differences in characteristics of the TAP in isolated superfused and arterially perfused canine right atrial (RA) preparations under baseline, rapidly activating delayed rectifier K+ current ( IKr) block, and combined block of ultrarapid delayed rectifier and transient outward K+ current ( IKur/ Ito block). Superfused preparations that survived generally displayed a triangle-shaped TAP. Exceptions included cells from the crista terminalis, where TAPs with a normal plateau could be recorded. In contrast, most TAPs recorded from throughout the perfused RA displayed a spike-and-dome and/or plateau morphology. The perfused RA displayed a heterogeneous distribution of repolarization, Vmax, and spike-and-dome morphology along the epicardial and endocardial surfaces as well as transmurally, in the region of the upper crista terminalis. IKr block with E-4031 prolonged repolarization homogeneously in the perfused RA, whereas IKur/ Ito block using low concentrations of 4-aminopyridine abbreviated action potential duration at 90% repolarization heterogeneously, leading to a reduction in dispersion of repolarization. Our data indicate that the electrical heterogeneities, previously described for the canine ventricle, also exist within the atria and that IKr block does not accentuate and IKur/ Ito block reduces RA dispersion of repolarization. Our study also points to major differences in the transmembrane activity recorded using superfused vs. arterially perfused atrial preparations.

Effects of Resibufogenin from Toad Venom on Isolated Purkinje Fibers

Chan su (dried toad venom) is a traditional Chinese medicine obtained from the skin venom gland of the toad. Chan su has long been used as a therapeutic agent in China and other Asian countries. Recent reports indicate that Chen su toxicity carries a high mortality rate in the United States. This study focused upon the cardiac electrophysiological and electro-toxicity effects of resibufogenin (RBG), one of the major components in Chan su. Action potentials of isolated sheep and canine heart Purkinje fibers were studied using glass microelectrode recording techniques. The results indicate that RBG significantly affected all parameters of transmembrane action potential, induced delayed after depolarization, and triggered arrhythmias in sheep and canine Purkinje fibers.

Modulation of the effects of sotalol on Purkinje strand electromechanical characteristics

The modulation of the effects of sotalol (30 μM) by two sodium channel blockers, tetrodotoxin (0.07 μM) and lidocaine (50 μM), and by a potassium channel activator, nicorandil (30 μM), were examined. Sotalol alone greatly increased Purkinje fiber transmembrane action potential duration and, in some preparations, induced early afterdepolarizations. Concurrent with the changes in action potential duration, sotalol also increased isolated Purkinje strand developed force paced at slow rates (0.33 Hz). These sotalol-induced alterations of Purkinje strand electromechanical characteristics were similar to those produced by either veratrine (0.6 or 1.0 μg/mL) or by tetraethylammonium (10 mM). The effects of sotalol on action potential duration and force development were reversed by exposure to either tetrodotoxin or nicorandil. Lidocaine also reversed the effects of sotalol on action potential duration and developed force. The sotalol-induced increase in action potential duration and development of early afterdepolarizations may, therefore, be abated by combination with drugs that either block cardiac sodium channels or that increase membrane potassium conductance. Combination with such drugs may help prevent the adverse arrhythmogenic effects of sotalol.Key words: sotalol, lidocaine, action potential duration, nicorandil, force development, tetrodotoxin.