title: Cardiotoxicity of emetine dihydrochloride by calcium channel blockade in isolated preparations and ventricular myocytes of guinea-pig hearts.
abstract: 1. The cardiotoxic effects of emetine dihydrochloride on mechanical and electrical activity were studied in isolated preparations (papillary muscles, sinoatrial and atrioventricular nodes, ventricular myocytes) of the guinea-pig heart. 2. Force of contraction was measured isometrically, action potentials and maximum rate of rise of the action potential were recorded by means of the intracellular microelectrode technique. Single channel L-type calcium current (Ba2+ ions as charge carrier) was studied with the patch-clamp technique in the cell-attached mode. 3. Emetine dihydrochloride (8-256 microM) reduced force of contraction in papillary muscles and spontaneous activity of sinoatrial and atrioventricular nodes concentration-dependently; the negative inotropic effect was abolished when the extracellular Ca2+ concentration was increased. 4. Maximum diastolic potential, action potential amplitude, maximum rate of rise of the action potential and the slope of the slow diastolic depolarization were decreased by emetine in sinoatrial as well as atrioventricular noes, while action potential duration was prolonged in both preparations (1-64 microM). 5. The amplitude of the L-type calcium single channel current was not altered by emetine dihydrochloride, while average open state probability was decreased concentration-dependently (10, 30 and 60 microM). 6. The most prominent effect of emetine dihydrochloride on single channel current was an increase of sweeps without activity. 7. At 60 microM, emetine dihydrochloride caused a decrease of the mean open time an increase of the mean closed time. The number of openings per record and number of bursts per record were reduced. 8. It is concluded that emetine dihydrochloride produces an L-type calcium channel block which might contribute to its cardiac side effects.
authors.affiliation: Institute of Pharmacology and Toxicology, Pharmazie-Zentrum, Vienna, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Lemmens-Gruber
authors.forename: A
authors.initials: A
authors.lastname: Karkhaneh
authors.forename: C
authors.initials: C
authors.lastname: Studenik
authors.forename: P
authors.initials: P
authors.lastname: Heistracher
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001283:Atrioventricular Node / Q000166:cytology / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000633:toxicity*; D004640:Emetine / Q000633:toxicity*; D005260:Female; D006168:Guinea Pigs; D006331:Heart Diseases / Q000139:chemically induced* / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology*; D010210:Papillary Muscles / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000633:toxicity*; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D011500:Protein Synthesis Inhibitors; D004640:Emetine