Inhibition of ATP-sensitive potassium channels in cardiac myocytes by the novel class III antiarrhythmic agent MS-551.
The novel class III antiarrhythmic agent, MS-551, has recently been shown to attenuate the decrease in ventricular effective refractory period and to prevent the subsequent ventricular fibrillation induced by pinacidil and hypoxia in isolated perfused rabbit hearts (Friedrichs et al. 1994). We studied the effects of MS-551 on single ATP-sensitive potassium channels in isolated rabbit ventricular myocytes using standard patch-clamp methods. MS-551 in the range from 1 microM to 100 microM produced a concentration-dependent reduction of the open probability of the ATP-sensitive potassium channel, with an apparent ED50 of 30 microM. This reduced channel activity was due to a smaller number of channel openings per unit time, and the average duration of each opening of the channel was unaffected. This property of MS-551 is likely to be of most significance in ischaemic tissue, where the ATP-sensitive channels are thought to carry the predominant current that shortens the duration of the action potential.
Martin
D K
DK
Department of Cardiology, St. Vincent's Hospital, Darlinghurst, Sydney N.S.W. Australia.
Nakaya
Y
Y
Wyse
K R
KR
Bursill
J A
JA
West
P D
PD
Campbell
T J
TJ
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009206:Myocardium / Q000737:chemistry* / Q000166:cytology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D011744:Pyrimidinones / Q000494:pharmacology*; D011817:Rabbits; D012044:Regression Analysis
D000889:Anti-Arrhythmia Agents; D015221:Potassium Channels; D011744:Pyrimidinones; C076259:nifekalant; D000255:Adenosine Triphosphate