Tedisamil inactivates transient outward K+ current in rat ventricular myocytes.
The action of tedisamil, a new bradycardiac agent with antiarrhythmic properties, was investigated in single rat ventricular myocytes using the whole cell voltage-clamp technique. Under current clamp conditions, 1-20 microM tedisamil caused marked prolongations of the action potential. Over the same concentration range, in voltage-clamped myocytes, tedisamil suppressed the transient outward current (ito) and enhanced its inactivation in a dose-dependent manner. The half-maximal dose for the effect of tedisamil on ito was approximately 6 microM. Tedisamil had no significant effects on the inwardly rectifying potassium current and calcium current but did suppress the sodium current at concentrations greater than 20 microM. Our findings suggest that tedisamil represents a new type of antiarrhythmic agent that primarily suppresses the transient outward K+ current.
Dukes
I D
ID
Department of Physiology, University of Pennsylvania, Philadelphia 19104-6085.
Morad
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents; D003521:Cyclopropanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles; D007425:Intracellular Membranes / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D011188:Potassium / Q000502:physiology*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D002316:Cardiotonic Agents; D003521:Cyclopropanes; D015222:Sodium Channels; C059921:tedisamil; D011188:Potassium; D002118:Calcium