Skeletal muscle adaptation in response to voluntary running in Ca 2+/calmodulin-dependent protein kinase IV-deficient mice

Takayuki Akimoto, Thomas J. Ribar, R. Sanders Williams, Zhen Yan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)


Mammalian skeletal muscles undergo adaptation in response to alteration in functional demands by means of a variety of cellular signaling events. Previous experiments in transgenic mice showed that an active form of Ca 2+/calmodulin-dependent protein kinase IV (CaMKIV) is capable of stimulating peroxisome proliferator-activated receptor γ-coactivator 1α (PGC-1α) gene expression, promoting fast-to-slow fiber type switching and augmenting mitochondrial biogenesis in skeletal muscle. However, a role for endogenous CaMKIV in skeletal muscle has not been investigated rigorously. We report that genetically modified mice devoid of CaMKIV have normal fiber type composition and mitochondrial enzyme expression in fast-twitch skeletal muscles and responded to long-term (4 wk) voluntary running with increased expression of myosin heavy chain type IIa, myoglobin, PGC-1α, and cytochrome c oxidase IV proteins in plantaris muscle in a manner similar to that of wild-type mice. Short-term motor nerve stimulation (2 h at 10 Hz) likewise increased PGC-1α mRNA expression in tibialis anterior muscles in both Camk4-/- and wild-type mice. In addition, we have confirmed that no detectable CaMKIV protein is expressed in murine skeletal muscle. Thus CaMKIV is not required for the maintenance of slow-twitch muscle phenotype and endurance training-induced mitochondrial biogenesis and IIb-to-IIa fiber type switching in murine skeletal muscle. Other protein kinases sharing substrates with constitutively active CaMKIV may function as endogenous mediators of activity-dependent changes in myofiber phenotype.

Original languageEnglish
Pages (from-to)C1311-C1319
JournalAmerican Journal of Physiology - Cell Physiology
Issue number5 56-5
Publication statusPublished - 2004 Nov
Externally publishedYes


  • Cellular signaling
  • Fiber type switching
  • Mitochondrial biogenesis
  • Proliferator-activated receptor γ-coactivator 1α

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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