Effects of sematilide, a novel class III antiarrhythmic agent, on membrane currents in rabbit atrial myocytes.
The effects of sematilide, a novel class III antiarrhythmic agent, on membrane currents were examined in single myocytes isolated from the rabbit left atrium, using the whole-cell voltage clamp technique. Application of 10, 30, 100 and 300 microM sematilide caused a concentration-dependent inhibition of the delayed rectifier K+ current (IC50 approx. 25 microM). The sematilide-sensitive current, which was recorded by means of a triangular voltage command, showed a strong inward rectification and had a peak at about -40 mV, suggesting that sematilide inhibits the rapidly activating delayed rectifier K+ current. The Ca2+-independent transient K+ and the inward rectifier K+ currents were not affected significantly by application of 100 microM sematilide. Moreover, voltage-dependent Na+ and Ca2+ currents were not affected significantly by 100 microM sematilide. These findings indicate that sematilide selectively blocks the rapidly activating delayed rectifier K+ current in atrial myocytes and provide evidence supporting the usefulness of the drug as a class III antiarrhythmic agent.
Ishii
Y
Y
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
Muraki
K
K
Kurihara
A
A
Imaizumi
Y
Y
Watanabe
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002469:Cell Separation; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011342:Procainamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D011817:Rabbits; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D007473:Ion Channels; D015221:Potassium Channels; D015222:Sodium Channels; C062818:sematilide; D011342:Procainamide; D002118:Calcium