Proposed schematic representation of the signal transduction mechanism leading to cardioprotection by pharmacological and ischemic preconditioning of the human myocardium. Upon activation of sarcolemmal receptors mitoKATP channels are opened via G proteins and possibly PKC-δ. The opening of mitoKATP channels will activate PKC possibly via the production of radical oxygen species (ROS). PKC may then translocate to various cellular sites including the mitochondria, sarcolemma and intercalated discs, and nucleus, a phenomenon that may involve specific PKC isoforms, where p38MAPK will be activated. In turn, p38MAPK may activate a single or multiple end-effectors directly or via MAPK intermediates. PLC: phospholipase C, PLD: phospholipase D.