Regulation of Contraction in Striated Muscle

摘要: Ca(2+) regulation of contraction in vertebrate striated muscle is exerted primarily through effects on the thin filament, which regulate strong cross-bridge binding to actin. Structural and biochemical studies suggest that position tropomyosin (Tm) troponin (Tn) filament determines interaction myosin with sites These can be characterized as blocked (unable bind cross bridges), closed (able weakly or open bridges so they subsequently isomerize become strongly bound release ATP hydrolysis products). Flexibility Tm may allow variability actin (A) affinity for along other than a single 7 actin:1 tropomyosin:1 (A(7)TmTn) regulatory unit. regulated by occupancy NH-terminal TnC, conformational changes resulting from binding, interactions among Tn, Tm, well S1 TnC enhances TnC-TnI interaction, weakens TnI attachment its 1-2 actins unit, increases movement over surface, exposes myosin-binding previously Tm. Adjacent are coupled their overlap regions where also controlled TnT. TnT interacts Ca(2+)-dependent manner. All these vary different protein isoforms. The surface "open" probability some configuration available isomerization force-producing states. In skeletal muscle, cycling promotes additional movement. This effectively stabilizes allows cooperative activation possibly neighboring A(7)TmTn units. structural findings support physiological observations steady-state transient mechanical behavior. Physiological following. 1) Tn/Tm bind. 2) regulates M.ADP.P(i) actin, precedes production force (and/or shortening) products. 3) initial rate development depends mostly extent kinetic properties but little level. 4) A small number attached within an unit activate one perhaps those results states production. 5) rates product steps per se (as indicated unloaded shortening velocity) early largely independent ([Ca(2+)]) beyond given baseline However, greater shortening, depend 6) cooperativity between units contributes does not affect development. 7) Strongly attached, delay relaxation 8) enhance cardiac influence lesser extent. 9) Different Tn subunit isoforms modulate detachment shown mutant proteins myotubes vitro motility assays. (ABSTRACT TRUNCATED)