Integrin and cytoskeletal involvement in signalling cell volume changes to glutamine transport in rat skeletal muscle

1 Muscle glutamine transport is modulated in response to changes in cell volume by a mechanism dependent on active phosphatidylinositol 3‐kinase. We investigated the possibility that this mechanism requires interactions between the extracellular matrix (ECM), integrins and the cytoskeleton as components of a mechanochemical transduction system. 2 Using skeletal muscle cells, we studied effects of (a) inactivating integrin‐substratum interactions by using integrin‐binding peptide GRGDTP with inactive peptide GRGESP as control, and (b) disrupting the cytoskeleton using colchicine or cytochalasin D, on glutamine transport after brief exposure to hypo‐osmotic, isosmotic or hyperosmotic medium (170, 300 and 430 mosmol kg−1, respectively). 3 Neither GRGDTP nor GRGESP significantly affected basal glutamine uptake (0.05 mm; 338 ± 58 pmol min−1 (mg protein)−1) but GRGDTP specifically prevented the increase (71 %) and decrease (39 %) in glutamine uptake in response to hypo‐ and hyperosmotic exposure, respectively. 4 Colchicine and cytochalasin D prevented the increase and decrease in glutamine uptake in response to changes in external osmolality. They also increased basal glutamine uptake by 59 ± 19 and 85 ± 16 %, respectively, in a wortmannin‐sensitive manner. 5 These results indicate involvement of ECM‐integrin‐mediated cell adhesion and the cytoskeleton in mechanochemical transduction of cell volume changes to chemical signals modulating glutamine transport in skeletal muscle. Phosphatidylinositol 3‐kinase may function to maintain the mechanotransducer in an active state.