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Repression of slow myosin heavy chain 2 gene expression in fast skeletal muscle fibers by muscarinic acetylcholine receptor and Gq signaling

Department of Cell Biology and Anatomy, Chicago Medical School, North Chicago, IL 60064

Address correspondence to Joseph X. DiMario, Dept. of Cell Biology and Anatomy, Chicago Medical School, 3333 Green Bay Rd., North Chicago, IL 60064. Tel: (847) 578-8633. Fax: (847) 578-3253. email: dimarioj{at}finchcms.edu

Gene expression in skeletal muscle fibers is regulated by innervation and intrinsic fiber properties. To determine the mechanism of repression of slow MyHC2 expression in innervated fast pectoralis major (PM) fibers, we investigated the function of the muscarinic acetylcholine receptor (mAchR) and Gq. Both mAchR and Gq are abundant in medial adductor (MA) and PM fibers, and mAchR and Gq interact in these fibers. Whereas innervation of PM fibers was insufficient to induce slow MyHC2 expression, inhibition of mAchR activity with atropine in innervated PM fibers induced slow MyHC2 expression. Increased Gq activity repressed slow MyHC2 expression to nondetectable levels in innervated MA fibers. Reduced mAchR activity decreased PKC activity in PM fibers, and increased Gq activity increased PKC activity in PM and MA fibers. Decreased PKC activity in atropine-treated innervated PM fibers correlated with slow MyHC2 expression. These data suggest that slow MyHC2 repression in innervated fast PM fibers is mediated by cell signaling involving mAchRs, Gq, and PKC.

Key Words: mAchR; innervation; fiber type; MyHC; PKC

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