Sponsor
Portland State University. Department of Physics
First Advisor
Jonathan Abramson
Date of Publication
Summer 10-1-2013
Document Type
Thesis
Degree Name
Master of Science (M.S.) in Physics
Department
Physics
Language
English
Subjects
Ryanodine -- Receptors, Catecholamines -- Physiological effect, Heart -- Metabolism
DOI
10.15760/etd.1438
Physical Description
1 online resource (vi, 70 pages)
Abstract
The cardiac ryanodine receptor (RyR2) is a Ca2+ ion channel found in the sarcoplasmic reticulum (SR), an intracellular membranous Ca2+ storage system. It is well known that a destabilization of RyR2 can lead to a Ca2+ flux out of the SR, which results in an overload of intracellular Ca2+; this can also lead to arrhythmias and heart failure. The catecholamines play a large role in the regulation of RyR2; stimulation of the Beta-adrenergic receptor on the cell membrane can lead to a hyperphosphorylation of RyR2, making it more leaky to Ca2+. We have previously shown that strong electron donors will inhibit RyR2. It is hypothesized that the catecholamines, sharing a similar structure with other proven inhibitors of RyR2, will also inhibit RyR2. Here we confirm this hypothesis and show for the first time that the catecholamines, isoproterenol and epinephrine, act as strong electron donors and inhibit RyR2 activity at the single channel level. This data suggests that the catecholamines can influence RyR2 activity at two levels. This offers promising insight into the potential development of a new class of drugs to treat heart failure and arrhythmia; ones that can both prevent the hyperphosphorylation of RyR2 by blocking the Beta;-adrenergic receptor, but can also directly inhibit the release of Ca2+ from RyR2.
Rights
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Persistent Identifier
http://archives.pdx.edu/ds/psu/10092
Recommended Citation
Klipp, Robert Carl, "Catecholamine Interactions with the Cardiac Ryanodine Receptor" (2013). Dissertations and Theses. Paper 1439.
https://doi.org/10.15760/etd.1438