title: The electrophysiologic effects of tolamolol (UK-6558-01) on the passive membrane properties of mammalian cardiac Purkinje fibers.
abstract: Tolamolol (UK-6558-01) is a relatively cardioselective beta receptor antagonist which is effective clinically in the treatment of supraventricular and ventricular arrhythmias. Animal studies suggest tolamolol may have significant antifibrillatory properties. The effect of tolamolol on the passive membrane properties of sheep cardiac Purkinje fibers was studied using multiple microelectrode techniques. In sodium-deficient Tyrode's solution, we measured the resting transmembrane voltage (Vr) at differing external potassium concentrations (K+]0, investigated current-voltage relationships and per formed cable analysis. Tolamolol was found to hyperpolarize the membrane in the presence of a large driving force [i.e., when (Vr - VK) was significantly greater than zero, where VK is the potassium equilibrium voltage ]; to hyperpolarize fibers with a Vr decreased due to stretch at [K+]0 = 4.0 mM; to increase membrane chord and slope potassium conductance; to decrease the membrane length constant; and to decrease the membrane time constant. In normal sodium Tyrode's solution, tolamolol could suppress automaticity. These results suggest that tolamolol increases membrane potassium conductance within the range of the pacemaker potential. This action can account, in part, for its ability to suppress automaticity and for its ability to prevent reentrant arrhythmias. In normal sodium Tyrode's solution, tolamolol suppressed oscillatory and sustained rhythmic activity occurring at a low transmembrane voltage which may be related to its alleged antifibrillatory effects.
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D012756:Sheep; D012964:Sodium / Q000502:physiology
chemical_list: D011412:Propanolamines; D012964:Sodium; D011188:Potassium