MODULATION OF GLYCOGEN-SYNTHESIS IN RAT SKELETAL-MUSCLE BY CHANGES INCELL-VOLUME

1. The hypothesis that cellular hydration state modulates muscle glyco gen synthesis was tested by measuring the incorporation of [C-14]gluco se into glycogen (glycogen synthesis) in primary rat myotubes after ex perimentally induced volume changes. 2. Glycogen synthesis in myotubes increased (by 75%, P<0 . 01) after swelling induced by 60 min exposur e to hyposmotic media (170 mosmol kg(-1)) relative to isosmotic contro l (300 mosmol kg(-1)) values; it decreased (by 31%, P<0 . 05) after sh rinkage induced by 60 min exposure to hyperosmotic (430 mosmol kg(-1)) media. Myotube 2-deoxy-D-glucose (0 . 05 mM) uptake was unaffected by changes in external osmolality. 3. Wortmannin (100 nM; 60 min), a pho sphatidylinositol S-kinase inhibitor, decreased basal glycogen synthes is by 28% whereas rapamycin (100 nM; 60 min), which blocks the activat ion of p70 S6 kinase, had no effect. Both wortmannin (100 nM; 60 min) and rapamycin (100 nM; 60 min) blocked the changes in glycogen synthes is resulting from hypo- and hyperosmotic exposure. 4. Myotube glycogen synthesis is modulated by volume changes independently of changes in glucose uptake. The phenomenon may be physiologically important in pro moting glycogen storage during circumstances of myofibrillar swelling, e.g. after feeding or exercise.