Electrophysiological and antiarrhythmic effects of the K‐channel opener, BRL 34915, in cardiac purkinje fibers

The effects of BRL 34915 (6cyano‐3,4‐dihydro‐2,2‐dimethyl‐trans‐4‐[2‐oxo‐1‐pyrrolidyl]‐2H‐benzo[b]pyran‐3‐ol, to be referred to as BRL) on the electromechanical properties of superfused dog and sheep ventricular Purkinje fibers were studied in vitro. At 5 μM, BRL shortened the action potential and decreased contractile force; these effects were greater in dog than in sheep Purkinje fibers. BRL reduced the slope and amplitude of diastolic depolarization measured during interruptions of drive. BRL suppressed spontaneous activity and antagonized the enhancement of automatic discharge induced by norepinephrine (0.5 μM), barium (50 μM), or strophanthidin (0.5 μM). BRL reduced or abolished the oscillatory potentials induced by high [Ca2+]o (10.8 mM). It also antagonized the spontaneous responses in low [K+]o (1 mM) and hyperpolarized fibers depolarized in a K‐free solution. It is concluded that BRL modifies the action potential and force and has antiarrhythmic actions as it antagonizes abnormal pacemaker activity in Purkinje fibers by modifying potassium conductance and secondarily reducing intracellular calcium.