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- W2913146561 abstract "In isolated thick filaments from cardiac muscle in relaxing conditions the myosin motors take up a quasi-helical arrangement on the filament surface in a conformation that inhibits their ATPase, known as the super-relaxed or OFF-state, suggesting that contraction of cardiac muscle requires activation of the thick filament in addition to calcium-induced activation of the thin filament. Here we characterised the OFF-to-ON structural transition in the cardiac thick filament induced by cooling from 37°C to 9°C by X-ray diffraction from intact and demembranated trabeculae isolated from rat hearts. Thick filament structure in demembranated trabeculae in relaxing solution in the presence of 3% dextran T500 at 27-37°C was similar to that in intact quiescent trabeculae. Maximal calcium activation at 27°C was used as a reference for the ON-state. Cooling of intact quiescent trabeculae induced a decrease in the intensity of the meridional myosin-based reflections and of the first myosin layer line, indicating disruption of the OFF-state of the thick filament. This was accompanied by an increase in the spacing of the M6 reflection associated with the axial periodicity of the thick filament backbone (SM6), a biphasic change in that of the M3 reflection associated with the myosin motors (SM3), and an increase in the equatorial intensity ratio (I11/I10) associated with the mass distribution of myosin motors within the filament lattice. Cooling of demembranated trabeculae in relaxing solution showed larger changes in the intensity and spacing of the myosin-based reflections, and SM3, SM6 and I11/I10 in relaxing solution at 9°C were close to the ON-state values. The results show that cooling to 9°C induces a structural OFF-to-ON transition in the thick filament, and the effect is larger in demembranated than in intact quiescent trabeculae. Supported by BHF, UK." @default.
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- W2913146561 date "2019-02-01" @default.
- W2913146561 modified "2023-10-18" @default.
- W2913146561 title "The Off-To-On Transition of Thick Filaments in Isolated Trabeculae from Rat Heart Induced by Cooling" @default.
- W2913146561 doi "https://doi.org/10.1016/j.bpj.2018.11.1429" @default.
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