MgADP activation contributes to force enhancement during fast stretch of isolated skeletal myofibrils

Biochem Biophys Res Commun. 2015 Aug 7;463(4):1129-34. doi: 10.1016/j.bbrc.2015.06.070. Epub 2015 Jun 19.

Abstract

Background: When an activated muscle is rapidly stretched, force rises and peaks while muscle lengthens. The peak force is normally called critical-force (Pc). The mechanism behind this increase in force is not well understood, but it has been associated with crossbridges operating in different states.

Methods: Myofibrils were attached between a cantilever and a micro-needle, and activated with Ca(2+) or MgADP. During activation, the myofibrils were stretched by 3% SLo at 10 SLo·s(-1). A crossbridge model was developed to better understand the effects of MgADP in myofibrils activation.

Results: Despite a similar stretch magnitude, MgADP activation produced a higher Pc (1.37 ± 0.07 P/Po) than Ca(2+) activation (Pc = 1.23 ± 0.03 P/Po). These results suggest that myofibrils activated with MgADP become stiffer than myofibrils activated with Ca(2+).

Conclusions: MgADP induces a fraction of crossbridges to form a "rigor-like" state that precedes ADP release, and that may not contribute to isometric forces. Such interpretation was strengthened by the results obtained with the developed crossbridge model, which showed that MgADP bias crossbridges into the rigor-like state. This state would be crucial to initiate a cooperative activation of crossbridges and actin, and to resist to unbinding from actin when the myofibrils are stretched.

Significance: Our results suggest a new mechanism contributing for force output during stretch, which underlies basic mechanisms of muscle contraction.

Keywords: AFM; Crossbridges; Force enhancement; MgADP; Myofibril.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / metabolism*
  • Animals
  • Calcium / metabolism
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiology*
  • Myofibrils / metabolism
  • Myofibrils / physiology*
  • Rabbits

Substances

  • Adenosine Diphosphate
  • Calcium