title: Co-operative interactions between troponin-tropomyosin units extend the length of the thin filament in skeletal muscle.
abstract: Ca2+ binding to troponin C (TnC), a subunit of the thin filament regulatory strand, activates vertebrate skeletal muscle contraction. Tension, however, increases with Ca2+ too abruptly to be the result of binding to sites on individual TnCs. Because extraction of one TnC on average per regulatory strand dramatically reduces the slope of the tension/Ca2+ relationship, we proposed that all 26 troponin-tropomyosin complexes of the regulatory strand form a co-operative system. This study of permeabilized (chemically skinned) rabbit psoas fibers analyzes the extraction time-course, the distribution of extraction sites on regulatory strands and the effects of extraction on the co-operativity of the tension/Ca2+ relationship. Two components of TnC are resolved in the time-course of extraction: a "rapidly extracting" component that can be selectively removed without affecting tension or co-operativity, and a "slow extracting" component whose loss reduces tension and co-operativity. Extraction of [14C]TnC shows that the slowly extracting component is lost randomly, so that, after removal of 5% of the TnC, most extracted strands have lost one TnC. Extraction interrupts the transmission of co-operativity by dividing the regulatory strand into smaller, independent co-operative systems; it reduces tension by preventing Ca2+ activation of TnC-depleted regulatory units. Co-operativity of the tension/Ca2+ relationship is modeled with the concerted-transition formalism for intact systems of 26 regulatory units, and for the smaller systems in extracted fibers.
authors: Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
authors: P W
authors: PW
authors: Brandt
authors: M S
authors: MS
authors: Diamond
authors: J S
authors: JS
authors: Rutchik
authors: F H
authors: FH
authors: Schachat
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D002118:Calcium / Q000378:metabolism; D007700:Kinetics; D046911:Macromolecular Substances; D009119:Muscle Contraction; D009132:Muscles / Q000378:metabolism*; D011817:Rabbits; D014335:Tropomyosin / Q000378:metabolism*; D014336:Troponin / Q000378:metabolism*; D019209:Troponin C
chemical_list: D046911:Macromolecular Substances; D014335:Tropomyosin; D014336:Troponin; D019209:Troponin C; D002118:Calcium