Characterizations of myosin essential light chain's N-terminal truncation mutant Δ43 in transgenic mouse papillary muscles by using tension transients in response to sinusoidal length alterations

J Muscle Res Cell Motil. 2013 May;34(2):93-105. doi: 10.1007/s10974-013-9337-x. Epub 2013 Feb 9.

Abstract

Cross-bridge kinetics were studied at 20 °C in cardiac muscle strips from transgenic (Tg) mice expressing N-terminal 43 amino acid truncation mutation (Δ43) of myosin essential light chain (ELC), and the results were compared to those from Tg-wild type (WT) mice. Sinusoidal length changes were applied to activated skinned papillary muscle strips to induce tension transients, from which two exponential processes were deduced to characterize the cross-bridge kinetics. Their two rate constants were studied as functions of ATP, phosphate (Pi), ADP, and Ca(2+) concentrations to characterize elementary steps of the cross-bridge cycle consisting of six states. Our results demonstrate for the first time that the cross-bridge kinetics of Δ43 are accelerated owing to an acceleration of the rate constant k 2 of the cross-bridge detachment step, and that the number of strongly attached cross-bridges are decreased because of a reduction of the equilibrium constant K 4 of the force generation step. The isometric tension and stiffness of Δ43 are diminished compared to WT, but the force per cross-bridge is not changed. Stiffness measurement during rigor induction demonstrates a reduction in the stiffness in Δ43, indicating that the N-terminal extension of ELC forms an extra linkage between the myosin cross-bridge and actin. The tension-pCa study demonstrates that there is no Ca(2+) sensitivity change with Δ43, but the cooperativity is diminished. These results demonstrate the importance of the N-terminal extension of ELC in maintaining the myosin motor function during force generation and optimal cardiac performance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / genetics
  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphate / genetics
  • Adenosine Triphosphate / metabolism
  • Animals
  • Calcium*
  • Kinetics
  • Mice
  • Mice, Transgenic
  • Myocardial Contraction*
  • Myosin Light Chains / genetics
  • Myosin Light Chains / metabolism*
  • Papillary Muscles / metabolism*
  • Papillary Muscles / pathology
  • Papillary Muscles / physiopathology*
  • Phosphates / metabolism
  • Sequence Deletion*

Substances

  • Myosin Light Chains
  • Phosphates
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Calcium