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Research AssociateAssistant ProfessorAssociate Research ScientistAssistant ProfessorAssociate ProfessorProfessorProfessor of Anatomy and Cell Biology
Primary Office: 1-324 Bowen Science BuildingIowa City, IA 52242
BA, Science, University of Tokyo, Tokyo, JapanPhysiology Course, Marine Biological Laboratory, Woods Hole, MAPhD, Biology, Princeton University, New Jersey
Post Doctoral, Columbia University, New York, New York
Biosciences Graduate ProgramDepartment of Anatomy and Cell Biology Graduate Program
Molecular mechanisms of contraction are probed using the method called "sinusoidal analysis" in skinned muscle fibers. With this system, force can be measured and the strain (length) sensitivity of the rate constants can be studied. In skinned fibers, the ions and molecules of experimental interest can be perfused into the lattice space, so that both mechanical and chemical perturbations can be applied at the same time. The experimental protocol is to perturb the fiber length during maximal Ca2+ activation, and the concomitant tension transients are recorded. The rate constants of transients are extracted and studied as functions of the ATP, ADP, and phosphate concentrations. From this information, the following crossbridge scheme (see below) consisting of seven states is deduced, together with the 10 kinetic constants that characterize the elementary steps. In this scheme, A=actin, M=myosin, S=ATP, D=ADP, and P=phosphate. With sinusoidal analysis, we investigated the elementary steps in rabbit psoas and soleus fibers, and in ferret and porcine myocardium. Our demonstration of the detailed crossbridge scheme was the first in a muscle fiber system. We also determined force on crossbridges in each state. Our investigations revealed that force is generated at step 4 with the isomerization of the AMDP state, and the same force is maintained with Pi release step 5. Our investigations demonstrated that force is generated as a result of hydrophobic interaction bet-ween the residues of actin and myosin. Future projects include research on substitution of contractile proteins to isoforms or to genetically engineered mutants.
Date Last Modified: 06/07/2014 -
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