The novel class III antiarrhythmics NE-10064 and NE-10133 inhibit IsK channels expressed in Xenopus oocytes and IKs in guinea pig cardiac myocytes.
Slowly activating, voltage-dependent IsK channels were expressed in Xenopus oocytes after injection of rat IsK protein cRNA and recorded with the two-microelectrode voltage-clamp technique. The IsK currents were inhibited by the new class III antiarrhythmic drugs NE-10064 and NE-10133. These compounds were equally potent in inhibiting a slowly activating potassium current (IKs) in guinea pig ventricular myocytes. No effects of these compounds could be observed on several other cloned delayed rectifier potassium channels, nor did they affect the inward rectifier current, IK1, in guinea pig cardiac myocytes at the concentrations tested. The blockade of IsK channels may contribute to the class III antiarrhythmic efficacy of these novel antiarrhythmics.
Busch
A E
AE
Oregon Health Sciences University, Portland 97201.
Malloy
K
K
Groh
W J
WJ
Varnum
M D
MD
Adelman
J P
JP
Maylie
J
J
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006827:Hydantoins; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014981:Xenopus
D000889:Anti-Arrhythmia Agents; D006827:Hydantoins; D007093:Imidazoles; D048289:Imidazolidines; D010879:Piperazines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011994:Recombinant Proteins; C088362:NE 10133; C086123:azimilide