Dynamic actin interaction of crossbridges: A general principle and its implications for crossbridge action in muscle

The oar-like crossbridge cycle, developed up to the mid-1970's, was shown to be inconsistent with more recent biochemical results. In crossbridge theories developed on the basis of the more recent kinetic schemes of the actomyosin ATPase in solution (Eisenberg and co-workers), however, the key elements proposed by Huxley (1957) were retained, one of which is the assumption that detachment of a force-generating crossbridge can only occur via completion of the ATPase cycle (release of ADP and rebinding of ATP). Furthermore, in these theories regulation is assumed to act by blocking/unblocking of a step subsequent to crossbridge attachment (e.g., P_i-release step). Both concepts, however, were recently shown to be in conflict with studies on skinned muscle fibers (still low ATPase activity at high-speed isotonic shortening, regulation acts via turnover kinetics and not recruitment (39)). By incorporation of the observed reversible actin interaction of crossbridges in all states, including the force-generating states, a working hypothesis can be developed (Fig. 5) which can account for the isotonic data. A mechanism by which such a scheme can also account for regulation via turnover kinetics was previously discussed (39).