Title

Regulation of striated muscle contraction: Effects of cross-bridge kinetics on calcium(2+) binding to troponin C

Date of Award

2003

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Physiology and Biophysics

First Committee Member

W. Glenn L. Kerrick, Committee Chair

Abstract

Striated muscle contraction is initiated by Ca2+ binding to troponin C (TnC). This Ca2+ binding causes a series of conformational changes in the regulatory proteins on the thin filament, leading to the formation of force generating cross-bridges, consequently force generation and/or shortening. Therefore, Ca2+ binding regulates cross-bridge formation; In turn, the cross-bridges may influence Ca2+ binding to TnC.In the present study, the hypothesis tested is that the cross-bridge kinetics influences Ca2+ binding to TnC in striated muscle. Mechanical length perturbations are used to change the cross-bridge kinetics, and their effects on Ca2+ binding to TnC are investigated by three different measurements; the intracellular Ca2+ changes, the Ca2+ sensitivity of force and ATPase activity, and the Ca2+ sensitivity of cTnCbadan fluorescence. When the dissociation rate of force generating cross-bridges is increased by mechanical length perturbations, a transient increase in the intracellular Ca 2+ in intact muscle, a reduced Ca2+ sensitivity of force and ATPase activity in skinned fibers, and a reduced Ca2+ sensitivity of the Ca2+ activated cTnCbadan fluorescence in cTnCbadan reconstituted fibers are observed. This suggests that the cross-bridge kinetic change can alter Ca2+ binding to TnC in striated muscle. A three-state model developed can explain all the results obtained in this thesis work.

Keywords

Biophysics, General

Link to Full Text

http://access.library.miami.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3081287