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  • Title: Roles of the calcineurin and CaMK signaling pathways in fast-to-slow fiber type transformation of cultured adult mouse skeletal muscle fibers.
    Author: Mu X, Brown LD, Liu Y, Schneider MF.
    Journal: Physiol Genomics; 2007 Aug 20; 30(3):300-12. PubMed ID: 17473216.
    Abstract:
    Two Ca2+-dependent signaling pathways, mediated by the Ca2+-activated phosphatase calcineurin and by the Ca2+-activated kinase Ca2+/calmodulin-dependent kinase (CaMK), are both believed to function in fast-to-slow skeletal muscle fiber type transformation, but questions about the relative importance of the two pathways still remain. Here, the differential gene expression during fast-to-slow fiber type transformation was studied using cultured adult flexor digitorum brevis (FDB) fibers and a custom minimicroarray system containing 21 fiber type-specific marker genes. After 3 days of culture, unstimulated fibers showed a generally slower gene expression profile; 3 days of electric field stimulation of cultured FDB fibers with a slow fiber-type pattern transformed the fibers to an even slower gene expression profile. Unstimulated FDB fibers overexpressing constitutively active calcineurin featured a slower gene expression profile, except four genes, indicating that transformation occurred, but was incomplete with activation of the calcineurin pathway alone. In both unstimulated FDB fibers and slow-type electrically stimulated FDB fibers, blocking of CaMK pathway with KN93 generated a faster gene expression profile compared with the negative control KN92, indicating that CaMK pathway functions during the transformation induced by both unstimulated culturing and slow fiber-type electrical stimulation. Moreover, neither the calcineurin nor the CaMK pathway alone could maximally activate the transformation, and coordination of the two pathways is required to accomplish a complete fast-to-slow fiber type transformation.
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