Activation of ATP-sensitive potassium channels by the predominant metabolite of isoflurane in rabbit ventricular myocytes.
- Author:
Jin HAN
1
;
Na Ri KIM
;
Eui Yong KIM
;
Sung Ju KIM
;
Kang Hee CHO
Author Information
1. Department of Physiology and Biophysics, College of Medicine, Inje University, 633-165 Gaegeum-dong, Busanjin-gu, Busan, South Korea. phykimey@ijnc.inje.ac.kr
- Publication Type:Original Article
- Keywords:
KATP channels;
Isoflurane;
Patch clamp techniques;
Rabbit ventricular myocytes
- MeSH:
Adenosine Triphosphate;
Heart;
Isoflurane*;
KATP Channels*;
Muscle Cells*;
Myocardial Ischemia;
Patch-Clamp Techniques;
Reperfusion;
Trifluoroacetic Acid
- From:The Korean Journal of Physiology and Pharmacology
2001;5(2):165-175
- CountryRepublic of Korea
- Language:English
-
Abstract:
Background: Recent in vivo experimental evidence suggests that isoflurane-induced cardioprotection may involve KATP channel activation. However, it was demonstrated that isofluran inhibited KATP channel activities in the inside-out patch mode. To explain this discrepancy, the present investigation tested the hypothesis that a metabolite of isoflurane, trifluoroacetic acid (TFA), contributes to isoflurnae-induced cardioprotection via KATP channel activation during myocardial ischemia and reperfusion. Methods: Single ventricular myocytes were isolated from rabbit hearts by an enzymatic dissociation procedure. Patch-clamp techniques were used to record single-channel currents. KATP channel activities were assessed before and after the application of TFA with the inside-out patch mode. Results: TFA enhanced channel activity in a concentration-dependent fashion. The concentration of TFA for half-maximal activation and the Hill coefficient were 0.03 mM and 1.2, respectively. TFA did not affect the single channel conductance of KATP channels. Analysis of open and closed time distributions showed that TFA increased burst duration and decreased the interburst interval without changes in open and closed time distributions shorter than 5 ms. TFA diminished ATP sensitivity of KATP channels in a concentration-response relationship for ATP. Conclusions: TFA, a metabolite of isoflurane, enhanced KATP channel activity in a concentration-dependent fashion. These results imply that TFA could mediate isoflurane-induced cardioprotection via KATP channel activation during myocardial ischemia and reperfusion.
