ELECTROPHYSIOLOGIC EFFECTS OF TOLAMOLOL (UK-6558-01) ON PASSIVE MEMBRANE PROPERTIES OF MAMMALIAN CARDIAC PURKINJE-FIBERS

  • 1 January 1976
    • journal article
    • research article
    • Vol. 199  (3) , 601-610
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 Na-deficient Tyrodes solution, the resting transmembrane voltage (Vr) was measured at differing Tyrodes solution, the resting transmembrane voltage (Vr) was measured at differing external K concentrations [K+]o, current-voltage relationships were investigated and cable analysis was performed. Tolamolol hyperpolarized the membrane in the presence of a large driving force [i.e., when (Vr - VK) was significantly greater than 0, where VK is the K equilibrium voltage]; hyperpolarized fibers with a Vr decreased due to stretch at [K+]0 = 4.0 mM; increased membrane chord and slope K conductance; decreased the membrane length constant; and decreased the membrane time constant. In normal Na Tyrodes solution, tolamolol could suppress automaticity. Tolamolol appears to increase membrane K 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 Na Tyrodes solution, tolamolol suppressed oscillatory and sustained rhythmic activity occurring at a low transmembrane voltage which may be related to its alleged antifibrillatory effects.

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