Research Interests

I am interested in the design principles that underlie the ability of muscle fibers to rapidly release calcium ions from the sarcoplasmic reticulum (SR) in the process of excitation-contraction coupling. Through comparative ultrastructural studies of skeletal and cardiac muscle, my laboratory has established the molecular architecture of the membranes involved in the initiation of calcium release. In skeletal muscle, the surface membrane channels responsible for sensing changes in transmembrane potential, the DHPRs,are intimately and precisely associated with the ryanodine receptors (RyRs). RyRs are the channels through which calcium is released from the SR. This relationship provides the basis for a molecular interaction allowing control of calcium release from the SR stores by events in the surface membrane. Interestingly, the same two components are not directly associated with each other in cardiac muscle and thus must interact via an intermediary agent, presumably calcium. Over the years, in have also been interested in the structure the myofibrils, and recently I have collaborated in rapid freezing experiments aimed at catching the myosin cross bridges in action.

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Section 23: Physiology and Pharmacology