Optimal length, calcium sensitivity and twitch characteristics of skeletal muscles from mdm mice with a deletion in N2A titin

Anthony L. Hessel, Venus Joumaa, Sydney Eck, Walter Herzog, Kiisa C Nishikawa

Research output: Contribution to journalArticle

Abstract

During isometric contractions, the optimal length of skeletal muscles increases with decreasing activation. The underlying mechanism for this phenomenon is thought to be linked to length dependence of Ca2+ sensitivity. Muscular dystrophy with myositis (mdm), a recessive titin mutation in mice, was used as a tool to study the role of titin in activation dependence of optimal length and length dependence of Ca2+ sensitivity. We measured the shift in optimal length between tetanic and twitch stimulation in mdm and wild-type muscles, and the length dependence of Ca2+ sensitivity at short and long sarcomere lengths in mdm and wild-type fiber bundles. The results indicate that the mdm mutation leads to a loss of activation dependence of optimal length without the expected change in length dependence of Ca2+ sensitivity, demonstrating that these properties are not linked, as previously suggested. Furthermore, mdm muscles produced maximum tetanic stress during sub-optimal filament overlap at lengths similar to twitch contractions in both genotypes, but the difference explains less than half of the observed reduction in active force of mdm muscles. Mdm muscles also exhibited increased electromechanical delay, contraction and relaxation times, and decreased rate of force development in twitch contractions. We conclude that the small deletion in titin associated with mdm in skeletal muscles alters force production, suggesting an important regulatory role for titin in active force production. The molecular mechanisms for titin's role in regulating muscle force production remain to be elucidated.

Original languageEnglish (US)
JournalThe Journal of experimental biology
Volume222
DOIs
StatePublished - Jun 17 2019

Fingerprint

Connectin
myositis
muscular dystrophy
Myositis
Muscular Dystrophies
skeletal muscle
Skeletal Muscle
muscle
calcium
Calcium
mice
contraction
Muscles
muscles
mutation
Sarcomeres
Mutation
Isometric Contraction
sarcomeres
genotype

Keywords

  • Activation-dependent properties
  • Connectin
  • Force transmission
  • Isometric force production
  • Length-dependent properties
  • Muscular dystrophy with myositis
  • Submaximal force production

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Physiology
  • Aquatic Science
  • Animal Science and Zoology
  • Molecular Biology
  • Insect Science

Cite this

Optimal length, calcium sensitivity and twitch characteristics of skeletal muscles from mdm mice with a deletion in N2A titin. / Hessel, Anthony L.; Joumaa, Venus; Eck, Sydney; Herzog, Walter; Nishikawa, Kiisa C.

In: The Journal of experimental biology, Vol. 222, 17.06.2019.

Research output: Contribution to journalArticle

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