Sponsor
Portland State University. Department of Physics
First Advisor
Jon Abramson
Date of Publication
1-1-2011
Document Type
Thesis
Degree Name
Master of Science (M.S.) in Physics
Department
Physics
Language
English
Subjects
Redox potential of RyR1, Calcium release channel, Ca²⁺, Myocardium, Sarcoplasmic reticulum, Ryanodine -- Receptors
DOI
10.15760/etd.430
Physical Description
1 online resource (v, 34 p.)
Abstract
The sarcoplasmic reticulum is an internal membrane system that controls the Ca²⁺ concentration inside muscle cells, and hence the contractile state of both skeletal and cardiac muscle. A key protein that that regulates the Ca²⁺ concentration in this membrane is known as the calcium release channel (CRC). The effects on Ca²⁺ dependent activation is of major importance in the study of CRC since other channel modifiers cannot effect the channel in the absence of Ca²⁺, or they require Ca²⁺ for maximum results. In this study of the high-affinity Ca²⁺ binding site, expected increases in total binding and shifts in the sensitivity of the channel to Ca²⁺ were observed when the pH increased or the solution redox status became more oxidative. Ranolazine, a drug used for treating Angina Pectoris (chest pain), desensitized the cardiac CRC activation but had no effect on the skeletal CRC. This selective desensitization may be the cause of Ranolazine's beneficial therapeutic effects. Both Ranolazine, and homocystein thiolactone (HCTL), a naturally occurring derivative of homocysteine, alters Ca²⁺ dependent activation by calcium without changing the number of channels found in the open state. Surprisingly the effect of HCTL was observed only in a reduced redox potential which leads to speculation that the formation of an alpha-carbon radical by HCTL on the cardiac CRC only occurs if select thiols are in a reduced state.
Rights
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Persistent Identifier
http://archives.pdx.edu/ds/psu/7373
Recommended Citation
Owen, Laura Jean, "Calcium and Redox Control of the Calcium Release Mechanism of Skeletal and Cardiac Muscle Sarcoplasmic Reticulum" (2011). Dissertations and Theses. Paper 430.
https://doi.org/10.15760/etd.430
Comments
Portland State University. Dept. of Physics