Protein Kinase C and Adenosine Synergistically Activate ATP-Sensitive Potassium Currents: Implications for Ischemic Preconditioning
- 43 Downloads
Several mechanisms have been proposed for the mechanism of ischemic preconditioning. Substantial evidence from studies involving rabbit hearts has shown that adenosine receptors, protein kinase C (PKC), and ATP-sensitive potassium (KATP) channels are involved.1’2 Furthermore, it has been suggested that these three hypotheses may be interrelated, with the KATP channel as the final effector.2 Opening of KATP channels shortens the action potential duration (APD). APD abbreviation reduces Ca2+ influx and contractility and thus conserves energy. If opening of KATP channels is the cause of the protection, the activity of KATP channels would need to be increased or primed by the initial preconditioning insult so that they would open more rapidly or to a greater extent during the subsequent ischemia. One explicit scheme2 proposes that adenosine receptor activation stimulates PKC during preconditioning; PKC then phosphorylates KATP channels and the phosphorylation makes the channel open more readily during the second ischemia. The protective effect of adenosine has been linked to KATP channel opening: The protection induced by preconditioning, adenosine receptor agonists and PKC activators can be eliminated by KATP channel blockers.2’3 Likewise, protection from preconditioning and adenosine receptor agonists can be blocked by PKC inhibitors.3 The present chapter summarizes our results examining the effect ofPKC and adenosine on KATPchannels in heart cells. The reader is referred to the full-length paper4 for details.
KeywordsAdenosine Receptor KATP Channel Ischemic Precondition Action Potential Duration Metabolic Inhibition
Unable to display preview. Download preview PDF.
- 1.Downey JM, Cohen MV, Ytrehus K. et al. Cellular mechanisms in ischemic preconditioning: the role of adenosine and protein kinase C, in Das DK (ed): Cellular, Biochemical, and Molecular Aspects of Reperfusion Injury. New York Academy of Sciences 1994;82–98.Google Scholar
- 2.Gross GJ, Yao Z, Auchampach JA. Role of ATP-sensitive potassium channels in ischemic preconditioning, in Przyklenk K, Kloner (ed). Ischemic Preconditioning: the Concepts of Endogenous Cardioprotection, Develop Cardiovasc Med. Vol 148. Boston: Kluwer Academic Publishers, 1994:125–135.CrossRefGoogle Scholar