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Characterizations of myosin essential light chain's N-terminal truncation mutant Delta 43 in transgenic mouse papillary muscles by using tension transients in response to sinusoidal length alterations
Journal article   Peer reviewed

Characterizations of myosin essential light chain's N-terminal truncation mutant Delta 43 in transgenic mouse papillary muscles by using tension transients in response to sinusoidal length alterations

Li Wang, Priya Muthu, Danuta Szczesna-Cordary and Masataka Kawai
Journal of muscle research and cell motility, Vol.34(2), pp.93-105
05/01/2013
DOI: 10.1007/s10974-013-9337-x
PMCID: PMC3656599
PMID: 23397074
url
https://www.ncbi.nlm.nih.gov/pmc/articles/3656599View
Open Access

Abstract

Cross-bridge kinetics were studied at 20 A degrees C in cardiac muscle strips from transgenic (Tg) mice expressing N-terminal 43 amino acid truncation mutation (Delta 43) 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 Ca2+ 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 Delta 43 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 Delta 43 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 Delta 43, 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 Ca2+ sensitivity change with Delta 43, 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.
Cell Biology Life Sciences & Biomedicine Science & Technology

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