Key Points
- To review the downstream cellular targets of ischemic preconditioning, focusing on the specific localization and protective role of ATP-sensitive potassium channels in myocardium.
- Literature synthesis examining cellular signaling pathways and protective mechanisms against ischemia and reperfusion injury.
- Evaluation of experimental evidence addressing sarcolemmal versus inner mitochondrial membrane localization of ATP-sensitive potassium channels.
- Upstream receptor activation and intermediate signal transduction pathways in ischemic preconditioning are well established, but downstream end-effector targets have remained contentious.
- Accumulating experimental data identify ATP-sensitive potassium channels on the mitochondrial inner membrane, rather than the sarcolemma, as the probable site mediating cytoprotection against ischemic damage.
Structured PICO
PPopulationCardiac cells (in the context of ischemia and reperfusion injury)
IInterventionIschemic preconditioning and K(ATP) channel activation
OOutcomeCytoprotection against ischemia and reperfusion injury
This review highlights that mitochondrial, rather than sarcolemmal, K(ATP) channels are likely the key downstream targets mediating cytoprotection during ischemic preconditioning.