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The Sarcoplasmic Reticulum (SR) is an internal membrane system found in muscle. By sequestering Ca2+ into its lumen, the SR decreases the cellular Ca2+ concentration and the muscle relaxes. By releasing its stores of Ca2+ through the ryanodine receptor (RyR), it triggers muscle contraction in both cardiac and skeletal muscle. In this seminar, I will discuss the chain of events that led to our discovery of the role of oxidative stress in muscle, and how redox reactions control the contractile state of muscle. More recently, we have observed that all RyR inhibitors are electron donors and that by increasing the electron donor properties of compounds known to interact with the RyR, we have been able to design new more potent inhibitors of the “Ca2+ leak” associated with the SR. In doing so we have developed new anti-arrhythmogenic drugs that are 100-1000 times more potent than presently exist. Our studies are an example of how fundamental research can lead to applications which have important biological and human relevance in the treatment of disease
About Professor Abramson
Research in Dr Abramson's laboratory is aimed at understanding the molecular mechanism underlying contraction and relaxation in skeletal and cardiac muscle. Special attention is focused on the calcium release protein of the sarcoplasmic reticulum. The effects of sulfhydryl oxidizing and reducing agents has been used to unravel the mechanism by which this protein gates and controls the contractile state of muscle. The mechanism of oxidative damage induced by ischemia and old age is also presently being examined as is the mechanism underlying skeletal muscle fatigue. Abramson has recently demonstrated that new more potent drugs designed to treat heart failure and muscle fatigue can be synthesized by modifying a drugs electron donor/acceptor properties. Designing new cardioprotective drugs has become a major focus of his laboratory. Abramson has also recently identified a new protein involved in congenital skeletal muscle disorders. His long term goal is to develop new methods for treating some forms of muscular dystrophy.
About the Department of Chemistry
The Portland State University Department of Chemistry maintains a teaching program of excellence at the undergraduate level and a gradute program emphasizing cutting-edge research in the chemistry of the environment, novel materials and biological systems. The Department's curriculum, faculty, library, and facilities of the department are approved by the American Chemical Society.