Portland State University. Department of Physics
Jonathan J. Abramson
Term of Graduation
Date of Publication
Master of Science (M.S.) in Physics
Naphthoquinone, Calcium channels, Sarcoplasmic reticulum
1 online resource (viii, 94 pages)
The sarcoplasmic reticulum (SR) is an intracellular membrane system which regulates cytoplasmic calcium concentration in muscle and controls the contractile state of muscle. In this thesis, the interaction between naphthoquinone and the Ca2+ release mechanism of SR is described. 1,4-naphthoquinone (1,4NQ) is shown to stimulate Ca2+ release and to modify high-affinity ryanodine binding to skeletal muscle sarcoplasmic reticulum. The interaction between 1,4NQ and the SR involves the oxidation ofcritical sulfhydryl groups associated with the Ca2+ release mechanism. The modulation of ryanodine binding by 1,4NQ is biphasic. At low concentrations of 1,4NQ (<10 >μM) ryanodine binding is stimulated, while at high concentrations (>10 μM) an inhibition of the ryanodine receptor (RyR) is observed. These studies reveal important characteristics of the RyR. There are at least two classes of functionally significant thiols associated with the RyR/Ca2+ release channel.
Oxidation of thiols induced by low concentrations of 1,4NQ activates the Ca2+ release mechanism. At higher concentrations of l,4NQ, oxidation of a second class of thiols inactivates the ryanodine receptor. A model is presented in which oxidation of reaction thiols leads to the opening of the Ca2+ release channel, while oxidation of a second set of thiols results in closure of the Ca2+ release channel.
Xia, Ruohong, "The Interaction of Naphthoquinones With the Calcium Release Channel of Skeletal Muscle Sarcoplasmic Reticulum" (1997). Dissertations and Theses. Paper 6327.