Functional significance of cardiac myosin essential light chain isoform switching in transgenic mice

Jason G. Fewell, Timothy Hewett, Atsushi Sanbe, Raisa Klevitsky, Eric Hayes, David Warshaw, David Maughan, Jeffrey Robbins

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

The different functions of the ventricular- and atrial-specific essential myosin light chains are unknown. Using transgenesis, cardiac- specific overexpression of proteins can be accomplished. The transgenic paradigm is more useful than originally expected, in that the mammalian heart rigorously controls sarcomeric protein stoichiometries. In a clinical subpopulation suffering from heart disease caused by congenital malformations of the outflow tract, an ELC1vAEELC1a isoform shift correlated with increases in cross-bridge cycling kinetics as measured in skinned fibers derived from the diseased muscle. We have used transgenesis to replace the ventricular isoform of the essential myosin light chain with the atrial isoform. The ELC1v→ELC1a shift in the ventricle resulted in similar functional alterations. Unloaded velocities as measured by the ability of the myosin to translocate actin filaments in the in vitro motility assay were significantly increased as a result of the isoform substitution. Unloaded shortening velocity was also increased in skinned muscle fibers, and at the whole organ level, both contractility and relaxation were significantly increased. This increase in cardiac function occurred in the absence of a hypertrophic response. Thus, ELC1a expression in the ventricle appears to be advantageous to the heart, resulting in increased cardiac function.

Original languageEnglish (US)
Pages (from-to)2630-2639
Number of pages10
JournalJournal of Clinical Investigation
Volume101
Issue number12
StatePublished - Jun 15 1998
Externally publishedYes

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Keywords

  • Heart
  • Hypertrophy
  • Mouse
  • Muscle
  • Sarcomere

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Fewell, J. G., Hewett, T., Sanbe, A., Klevitsky, R., Hayes, E., Warshaw, D., Maughan, D., & Robbins, J. (1998). Functional significance of cardiac myosin essential light chain isoform switching in transgenic mice. Journal of Clinical Investigation, 101(12), 2630-2639.