SODIUM-DEPENDENT GLUTAMATE TRANSPORT IN CULTURED RAT MYOTUBES INCREASES AFTER GLUTAMINE DEPRIVATION

Glutamine produced and stored in skeletal muscle is an important sourc e of nitrogen and energy for the whole body in health and disease and, unsurprisingly, glutamine turnover in muscle is subject to substantia l metabolic control. L-Glutamate, a necessary substrate for glutamine synthetase, is transported into muscle cells by Na+-dependent and -ind ependent transport systems. In primary cultures of rat skeletal muscle myotubes (a useful model system for studies of muscle metabolism and membrane transport), Na+-dependent glutamate transport (K(m) almost-eq ual-to 0.7 mM glutamate) shows adaptive up-regulation (65% increase in transport V(max) from 2.7 to 4.4 nmol . min-1 . mg protein-1) in cell s within 24 h of glutamine depletion (t1/2 for increase of almost-equa l-to 4 h), whereas Na+-independent glutamate uptake remains unaltered. Up-regulation of transport is suppressed by inhibitors of gene transc ription (actinomycin-D) and translation (cycloheximide) and is reverse d by glutamine supplementation. Increased glutamate transport capacity should provide extra substrate for glutamine synthesis in muscle cell s. Thus, in concert with previously discovered increases in cell gluta mine transport capacity and glutamine synthetase activity, it may repr esent part of a coordinated response to decreased glutamine availabili ty (e.g., under circumstances of increased glutamine utilization by ot her tissues in vivo).