Trifluoroacetic acid activates ATP-sensitive K(+) channels in rabbit ventricular myocytes.
Recent in vivo experimental evidence suggests that isoflurane-induced cardioprotection may involve K(ATP) channel activation during myocardial ischemia. The actual effect of isoflurane on cardioprotective ion conductance, however, such as that mediated by the opening of K(ATP) channels, has been the subject of some controversy in the past. The investigation reported here used a patch-clamp technique to test the hypothesis that a metabolite of isoflurane, trifluoroacetic acid (TFA), contributes to isoflurane-induced cardioprotection via K(ATP) channel activation. TFA enhanced channel activity in a concentration-dependent fashion, exhibiting half-maximal activation at 0.03 mM. TFA increased the number of openings of the channel, but did not affect the single channel conductance of K(ATP) channels. Analysis of open and closed time distributions showed that TFA increased the burst duration and decreased the interburst interval without eliciting changes of less than 5 ms in open and closed time distributions. TFA diminished the ATP sensitivity of K(ATP) channels in a concentration-response relationship for ATP. These results imply that TFA could mediate isoflurane-induced cardioprotection via K(ATP) channel activation during myocardial ischemia and reperfusion.
Han
J
J
Department of Physiology and Biophysics, College of Medicine, Inje University, 633-165 Gaegeum-Dong, Busanjin-Ku, Busan, 614-735, Korea.
Kim
N
N
Kim
E
E
D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D014269:Trifluoroacetic Acid / Q000494:pharmacology*
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D007530:Isoflurane; D014269:Trifluoroacetic Acid