Reactive oxygen species (ROS) have been implicated in the damage which occurs to the myocardium both during ischemia and reperfusion following an ischemic episode. One aspect to this damage is an alteration in the electrophysiological properties of the myocardium in a manner to produce arrhythmias. However, there is very little information regarding the effects ROS have on the electrophysiological properties of cardiac muscle. In the proposed studies, ROS will be produced by activating photosensitizers with light and the effects of the ROS on various electrophysiological parameters will be investigated. The studies will be done on single frog cardiac cells. The specific objectives of the project are to determine the following: 1) the effects of ROS on the resting potential, action potential, and specific ionic currents, 2) the dependency of these effects on the site of ROS production (inside vs. outside membrane surface), 3) the progression or reversibility of these effects following termination of ROS production, and 4) the dependency of the effects on the intensity and/or duration of ROS production. The results of this study will help clarify how ROS affect the ionic currents essential to the generation of the resting and action potential, and clarify the role of the site of ROS production in these effects. The study will also give insight into the cell's ability to rapidly repair the damage caused by ROS and whether or not ROS initiate reactions which further modify ionic currents after ROS production ceases. From these results, inferences can be made as to how ROS-induced alteration in the electrophysiological properties of the cardiac cell contribute to the generation of arrhythmias during ischemia and reperfusion.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Cardiovascular and Pulmonary Research A Study Section (CVA)
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University of Kansas
Schools of Medicine
Kansas City
United States
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Tarr, M; Arriaga, E; Valenzeno, D (1995) Progression of cardiac potassium current modification after brief exposure to reactive oxygen. J Mol Cell Cardiol 27:1099-109
Arriaga, E; Frolov, A; Tarr, M et al. (1994) Membrane ionic current photomodification by rose bengal and menadione: role of singlet oxygen. Photochem Photobiol 59:637-42
Tarr, M; Arriaga, E; Goertz, K K et al. (1994) Properties of cardiac I(leak) induced by photosensitizer-generated reactive oxygen. Free Radic Biol Med 16:477-84
Valenzeno, D P; Arriaga, E; Trank, J et al. (1993) Membrane potential can influence the rate of membrane photomodification. Photochem Photobiol 57:996-9