First Advisor

Keith Garlid

Term of Graduation

Spring 2008

Date of Publication

5-2008

Document Type

Thesis

Degree Name

Master of Science (M.S.) in Biology

Department

Biology

Language

English

Subjects

Potassium channels, Coronary heart disease -- Prevention, Myocardial infarction -- Prevention

Physical Description

1 online resource (2, v, 67 pages)

Abstract

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 [Greek symbol Psi]ϵRACK, 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 1 0nM, respectively). PKG and [Greek symbol Psi]ϵRACK, 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.

Rights

© 2008 Ksenia Andrukhiv Everton

In Copyright. URI: http://rightsstatements.org/vocab/InC/1.0/

This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).

Included in

Biology Commons

Share

COinS