Antiarrhythmic and electrophysiological effects of the novel KATP channel opener, rilmakalim, in rabbit cardiac cells.
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. Rilmakalim (0.24-7.2 microM) 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 microM) also decreased the APD of Purkinje fibers. 3. Rilmakalim (2.4 microM) and cromakalim (100 microM) hyperpolarized and abolished abnormal automaticity of cardiac Purkinje fibers pretreated with barium (0.2-0.3 mM). Glibenclamide (5 microM) blocked the hyperpolarizing effect. 4. Stable early afterdepolarizations induced in Purkinje fibers by berberine (100 microM) were reversibly blocked by rilmakalim (2.4 microM), which also suppressed late afterdepolarizations induced in Purkinje fibers treated with ouabain (0.3-0.5 microM). 5. The rate of spontaneous discharges of the rabbit sinoatrial node was not affected by rilmakalim (7.2 microM) or by pinacidil (100 microM). Both agents were also unable to affect the APD of atrial muscle fibers. 6. In cardiac Purkinje fibers, tetraethylammonium (TEA; 20 mM) significantly reduced the effects of rilmakalim (2. 4 microM) on the APD. However, neither TEA nor glibenclamide (100 microM) reduced the shortening of the APD induced by dinitrophenol (30 microM) or by salicylate (1 mM).
Riccioppo Neto
F
F
Department of Pharmacology, Faculty, of Medicine of Ribeirào Preto, University of Sào Paulo, Brazil.
Mesquita Júnior
O
O
Olivera
G B
GB
D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D015221:Potassium Channels / Q000187:drug effects*; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D011759:Pyrrolidines / Q000494:pharmacology*; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects* / Q000502:physiology; D012980:Sodium Salicylate / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D002839:Chromans; D015221:Potassium Channels; D011759:Pyrrolidines; D013757:Tetraethylammonium Compounds; C075012:rilmakalim; D019789:Tetraethylammonium; D019297:2,4-Dinitrophenol; D005905:Glyburide; D012980:Sodium Salicylate