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Ketamine abolishes ischemic preconditioning through inhibition of K(ATP) channels in rabbit hearts
1Department of Physiology and Biophysics, College of Medicine, Inje University, Busan 614-735, Korea.
Abstract:
Although ketamine inhibits ATP-sensitive K (K(ATP)) channels in rat ventricular myocytes and abolishes the cardioprotective effect of ischemic preconditioning in isolated rat hearts and in rabbits in in vivo, no studies to date specifically address the precise mechanism of this prevention of ischemic preconditioning by ketamine. This study investigated the mechanism of the blockade of ischemic preconditioning by ketamine in rabbit ventricular myocytes using patch-clamp techniques and in rabbit heart slices model for simulated ischemia and preconditioning. In cell-attached and inside-out patches, ketamine inhibited sarcolemmal K(ATP) channel activities in a concentration-dependent manner. Ketamine decreased the burst duration and increased the interburst duration without a change in the single-channel conductance. In the heart slice model of preconditioning, heart slices preconditioned with a single 5-min anoxia, pinacidil, or diazoxide, followed by 15-min reoxygenation, were protected against subsequent 30-min anoxia and 1-h reoxygenation, and the cardioprotection was blocked by the concomitant presence of ketamine. These data are consistent with the notion that inhibition of sarcolemmal or mitochondrial K(ATP) channels may contribute, at least in part, to the mechanism of the blockade of ischemic preconditioning by ketamine.
Insights
Ketamine blocks the heart-protective effects of ischemic preconditioning by inhibiting ATP-sensitive potassium (KATP) channels. This study reveals ketamine
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Cellular Electrophysiology
Background:
- Ketamine is known to inhibit ATP-sensitive potassium (KATP) channels.
- Ketamine abolishes the cardioprotective effects of ischemic preconditioning.
- The precise mechanism of ketamine's blockade of ischemic preconditioning remains unclear.
Purpose of the Study:
- To investigate the mechanism by which ketamine blocks ischemic preconditioning in rabbit ventricular myocytes.
- To elucidate the role of KATP channels in ketamine's cardioprotective blockade.
Main Methods:
- Patch-clamp techniques were used to study KATP channel activity in rabbit ventricular myocytes.
- A rabbit heart slice model was employed to simulate ischemia and preconditioning.
- Ketamine's effect on KATP channel activity and cardioprotection was assessed.
Main Results:
- Ketamine inhibited sarcolemmal KATP channel activity in a concentration-dependent manner.
- Ketamine altered KATP channel kinetics, decreasing burst duration and increasing interburst duration.
- Ketamine blocked the cardioprotective effects of ischemic preconditioning in rabbit heart slices.
Conclusions:
- Ketamine's inhibition of sarcolemmal KATP channels contributes to its blockade of ischemic preconditioning.
- Mitochondrial KATP channel inhibition may also play a role in ketamine's mechanism.
- These findings clarify the mechanism underlying ketamine's interference with cardioprotective preconditioning.
