Journal
PROCEEDINGS OF THE NUTRITION SOCIETY
Volume 63, Issue 2, Pages 279-286Publisher
C A B I PUBLISHING
DOI: 10.1079/PNS2004335
Keywords
calcium ions; Ca 2(+)/calmodulin-dependent kinase; skeletal muscle; mitochondrial biogenesis
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Intracellular Ca2+ plays an important role in skeletal muscle excitation-contraction coupling and also in excitation-transcription coupling. Activity-dependent alterations in muscle gene expression as a result of increased load (i.e. resistance or endurance training) or decreased activity (i.e. immobilization or injury) are tightly linked to the level of muscle excitation. Differential expression of genes in slow- and fast-twitch fibres is also dependent on fibre activation. Both these biological phenomena are, therefore, tightly linked to the amplitude and duration of the Ca2+ transient, a signal decoded downstream by Ca2+-dependent transcriptional pathways. Evidence is mounting that the calcineurin-nuclear factor of activated T-cells pathway and the Ca2+/calmodulin-dependent kinases (CaMK) 11 and IV play important roles in regulating oxidative enzyme expression, mitochondrial biogenesis and expression of fibre-type specific myofibrillar proteins. CaMKII is known to decode frequency-dependent information and is activated during hypertrophic growth and endurance adaptations. Thus, it was hypothesized that CaMKII, and possibly CaMKIV, are down regulated during muscle atrophy and levels of expression of CaMKIIalpha, -IIbeta, -IIgamma and -IV were assessed in skeletal muscles from young, aged and denervated rats. The results indicate that CaMKIIgamma, but not CaMKIIalpha or -beta, is up regulated in aged and denervated soleus muscle and that CaMKIV is absent in skeletal but not cardiac muscle. Whether CaMKIIgamma up-regulation is part of the pathology of wasting or a result of some adaptational response to atrophy is not known. Future studies will be important in determining whether insights from the adaptational response of muscle to increased loads will provide pharmacological approaches for increasing muscle strength or endurance to counter muscle wasting.
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