| The Effect of Trifluoroacetic Acid, a Metabolite of Isoflurane on the ATP-sensitive Potassium Channel in Rabbit Ventricular Myocytes. |
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Dong Jun Lee, Sung Joo Kim, Kyung Ho Ha, Mun Cheol Kim, Kang Hee Cho |
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Department of Anesthesiology, College of Medicine, Inje University, Seoul, Korea. kheecho@hitel.net |
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| Abstract |
BACKGROUND
Activation of ATP-sensitive K+ channels (KATP channels) in the cardiac muscle produces cardioprotective effects during myocardial ischemia. Previous experimental evidence indicates that volatile anesthetics exert beneficial actions in ischemic myocardium and enhance functional recovery of stunned myocardium. More recently, volatile anesthetics have been demonstrated to produce cardioprotective effects in stunned myocardium in vivo, and these effects are blocked by a KATP channel antagonist. This finding suggests that KATP channel activation by isoflurane may mediate antiischemic effects. However, it was demonstrated that isoflurane inhibited KATP channel activity in rabbit ventricular myocytes. To explain the discrepancy, the present investigation tested the hypothesis that isoflurane and its metabolite, trifluoroacetic acid, contributes to the activation of KATP channels in rabbit ventricular myocytes.
METHODS
Single ventricular myocytes were isolated from rabbit hearts by an enzymatic dissociation procedure.
Single-channel currents were measured in inside-out patch configurations of the patch-clamp technique. The perfusing liquid was equilibrated with isoflurane by passing 100% O2 through a vaporizer.
RESULTS
Isoflurane inhibited KATP channel activity without a change in the single-channel conductivity. Isoflurane decreased the burst duration and increased the interburst duration. In addition, isoflurane diminished the ATP sensitivity of KATP channels. Trifluoroacetic acid, a metabolite of isoflurane, enhanced the channel activity in a dose-dependent fashion. Trifluoroacetic acid increased the burst duration and decreased the interburst duration without a change in the single-channel conductivity. Isoflurane and trifluoroacetic acid diminished the ATP sensitivity of KATP channels.
CONCLUSIONS
These results imply that isoflurane and its metabolite could mediate cardioprotective effects via KATP channel activation during myocardial ischemia. |
| Key Words:
ATP-sensitive potassium (KATP) channel; myocardial ischemia; rabbit ventricular myocytes; isoflurane; patch-clamp techniques; trifluoroacetic acid |
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