Antiarrhythmic and electrophysiological effects of the novel K ATP channel opener, rilmakalim, in rabbit cardiac cells

Abstract

1. 1. The effects of rilmakalim, a potassium channel opener, were studied on rabbit cardiac Purkinje, ventricular muscle and atrial fibers, with the use of conventional microelectrode techniques. 2. 2. Rilmakalim (0.24-7.2 μM) shortened, in a concentration-dependent manner, the action potential duration (APD) in Purkinje and ventricular muscle without affecting other parameters of the action potential. Pinacidil (30–300 μM) also decreased the APD of Purkinje fibers. 3. 3. Rilmakalim (2.4 μM) and cromakalim (100 μM) hyperpolarized and abolished abnormal automaticity of cardiac Purkinje fibers pretreated with barium (0.2–0.3 mM). Glibenclamide (5 μM) blocked the hyperpolarizing effect. 4. 4. Stable early afterdepolarizations induced in Purkinje fibers by berberine (100 μM) were reversibly blocked by rilmakalim (2.4 μM), which also suppressed late afterdepolarizations induced in Purkinje fibers treated with ouabain (0.3–0.5 μM). 5. 5. The rate of spontaneous discharges of the rabbit sinoatrial node was not affected by rilmakalim (7.2 μM) or by pinacidil (100 μM). Both agents were also unable to affect the APD of atrial muscle fibers. 6. 6. In cardiac Purkinje fibers, tetraethylammonium (TEA; 20 mM) significantly reduced the effects of rilmakalim (2.4 μM) on the APD. However, neither TEA nor glibenclamide (100 μM) reduced the shortening of the APD induced by dinitrophenol (30 μM) or by salicylate (1 mM).