Cardiac electrophysiological effects of levosimendan, a new calcium sensitizer.
1. The conventional microelectrode and the patch-clamp techniques were used to study the electrophysiological effects of levosimendan, a new calcium-sensitizing cardiotonic drug, in cardiac ventricular muscle. 2. Levosimendan (5 microM) did not change the main repolarizing currents, such as the inward rectifier potassium, transient outward and the delayed rectifier outward potassium current, in rabbit ventricular myocytes. 3. In rabbit ventricular muscle, levosimendan, at relatively low concentrations (0.1-1 microM), did not change significantly the amplitude of the inward calcium current but increased the amplitude of the twitch tension. 4. In guinea pig ventricular muscle, levosimendan, at higher concentrations (1-5 microM), significantly increased the amplitude of the inward calcium current and the slow-response action potential parameters. 5. It is concluded that levosimendan, in addition to its calcium sensitizing properties characterized by "silent electrophysiology," exhibits cardiac electrophysiological effects similar to those of phosphodies-terase inhibitors.
Virág
L
L
Department of Pharmacology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Hála
O
O
Marton
A
A
Varró
A
A
Papp
J G
JG
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006835:Hydrazones / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology; D010210:Papillary Muscles / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011724:Pyridazines / Q000494:pharmacology*; D011817:Rabbits; D000077464:Simendan
D015220:Calcium Channels; D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D002118:Calcium