Portland State University. Environmental Sciences and Resources Ph. D. Program
Jonathan J. Abramson
Date of Award
Doctor of Philosophy (Ph.D.) in Environmental Sciences and Resources: Chemistry
Environmental Science and Management
1 online resource (3, x, 132 pages)
Sarcoplasmic reticulum, Calcium in the body
Skeletal muscle contains an internal membrane system called the sarcoplasmic reticulum (SR) whose function is to regulate the Ca2+ concentration of the myoplasm. Ca2+ is transported into the SR from the myoplasm via a Ca2+ dependent ATPase thus lowering the myoplasmic Ca2+ concentration. Ca2+ exits from the SR via a Ca2+ releqse pathway resultingin the increase of myoplasmic Ca2+. Muscles contract when the myoplasmic Ca2+ concentration is > 5 uM and relax when the Ca2+ concentration is lowered below 1 uM. The Ca2+ dependent ATPase has been extensively studied but the Ca2+ release system is less well understood.
SR vesicles release their internal Ca2+ when a reactive thiol group is oxidized (oxidation-induced Ca2+ release). It is shown in this dissertation that oxidation-induced Ca2+ release is stimulated by adenine nucleotides with an order of effectiveness of: ATP > AMP-PCP > cAMP > AMP > adenine. The stimulatory effect is not dependent upon phosphorylation of a protein because AMP-PCP, a nonhydrolyzable analogue of ATP, is almost as effective as ATP in stimulating oxidation-induced Ca2+ release.
It is also shown in this dissertation that photooxidation of histidyl residues results in an increase Ca2+ permeability of the SR. Unlike oxidation-induced Ca2+ release, photooxidation-induced Ca2+ release is Mg2+ independent, not inhibited by ruthenium red and inhibited by adenine nucleotides. Covalent modification of histidyl residues with ethoxyformic anhydride results in the increased permeability of SR vesicles. Similar to photooxidation-induced Ca2+ efflux, EFA-induced Ca2+ efflux is Mg2+ independent and is inhibited by ATP. The AMP-PCP protection of SR proteins from modification with EFA is similar to non-competitive inhibition with a KI = 50 uM. The photooxidation effect is not on membrane lipids but on a protein component which may be an ion transport system, other than the Ca2+ release protein, altered in such a way that it now transports Ca2+.
Stuart, Janice F., "Chemical Modification of Skeletal Muscle Sarcoplasmic Reticulum Vesicles: A Study of Calcium Permeability" (1989). Dissertations and Theses. Paper 1389.