Signaling elements involved in amino acid transport responses to altered muscle cell volume

Abstract

Skeletal muscle glutamine uptake via the transport system Nm is subject to rapid (t(1/2) = approximately 1 min) regulation after changes in cell volume by mechanisms that remain to be elucidated. Wortmannin (phosphatidylinositol 3-kinase inhibitor) but not rapamycin (inhibitor of p70S6 kinase activation) prevents both hypo-osmotic swelling-induced stimulation and hyperosmotic shrinkage-induced inhibition of Na+-dependent glutamine uptake in primary culture of rat skeletal muscle. G-protein inhibitors (cholera, pertussis toxins) also abolished responses of glutamine transport to cell volume changes whereas these responses were sustained in the presence of G-protein activators (MAS 7, lysophosphatidic acid). Swelling-induced activation of glutamine transport does not seem to involve release of autocrine factors because "conditioned" medium from swollen cells has no effect on previously unstimulated cells. System A amino acid transport exhibits responses to cell volume change that are opposite to those of system Nm, but these are also blocked by wortmannin. Active phosphatidylinositol 3-kinase appears to be required to enable muscle cells to exhibit rapid, volume-induced changes in amino acid transport when suitably stimulated.