Portland State University. Department of Biology
Term of Graduation
Date of Publication
Master of Science (M.S.) in Biology
Potassium channels, Coronary heart disease -- Prevention, Myocardial infarction -- Prevention
1 online resource (2, v, 67 pages)
Mitochondrial ATP-sensitive potassium channel (mitoKATP) has been suggested to be the mediator of cardiac preconditioning. All of the diverse pharmacological and physiological agents that open mitoKATP provide protection against ischemia-reperfusion injury. Some investigators have pointed out that some of these mitoKATP channel openers also inhibit succinate dehydrogenase (SDH), complex II of the electron transport chain. Based on this observation they suggest that it is the inhibition of SDH, and not the opening of mitoKATP channel, that mediates the observed cardioprotection. In this study, I examined four chemically distinct and unrelated pharmacological agents, diazoxide, 3-Nitropropionic Acid (3-NPA), Protein Kinase G (PKG), and ΨεRACK, all of which have been shown to open mitoKATP, to demonstrate that the said cardioprotective effect mediated by mitoKATP is entirely independent of SDH. Light scattering technique was utilized to measure the state of mitoKATP (open/closed) by measuring mitochondrial volume. An electrode that measures oxygen concentration was utilized to measure mitochondrial respiration. The results of this study confirm that two of the drugs, diazoxide and 3-NPA, inhibit succinate-supported respiration in high doses (IC50 = 140μM and IC50 = 1.05mM, respectively). Both of these drugs, however, do not inhibit succinate-supported respiration at the concentration necessary to open mitoKATP (30μM and 10nM, respectively). PKG and ΨεRACK, the other two mitoKATP openers tested in this study, do not inhibit succinate-supported respiration at any concentration tested. These results support the hypothesis that potassium channel openers mediate cardioprotection through the opening of mitoKATP and not through the inhibition of SDH.
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Everton, Ksenia Andrukhiv, "The Role of Mitochondria ATP-sensitive Potassium Channel in Cardioprotection" (2008). Dissertations and Theses. Paper 5829.