Mitochondrial Katp Channels

Opening of mitochondrial KATP channels (mitoKATP) with diazoxide induces neuronal preconditioning in vitro and in vivo (43-45), and blockade of mitoKATP opening with 5-hydroxydecanoate abolishes tolerance induction by ischemic preconditioning (46) and by chemical preconditioning using the mitochondrial enzyme SDH inhibitor 3-NPA (47). Diazoxide also leads to increased free-radical production, possibly by inhibiting SDH, which is part of complex II of the electron transport chain (45) . A burst of reactive oxygen species (ROS) might trigger preconditioning mechanisms of protection. For example, tolerance induction by 3-NPA also increases ROS production and induces tolerance to cerebral ischemia (48). SDH has recently been found to be part of a macromolecular complex that forms mitoKATP (49). Diazoxide and 3-NPA might, therefore, actually act on the same molecule, suggesting that different methods of preconditioning might eventually converge on a common pathway that leads to tolerance induction and neuroprotection.

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