Glutamine transport and metabolism in denervated rat skeletal muscle

H. S. Hundal, P. Babij, P. W. Watt, M. R. Ward, M. J. Rennie

Research output: Contribution to journalArticlepeer-review

Abstract

Rat skeletal muscle glutamine fell by 40% from 4.18 to 2.5 μmol/g wet weight (P < 0.01) after 4 days of denervation. Over the same period net glutamine efflux from denervated hindlimbs [i.e., arteriovenous (a-v) concentration differences x blood flow] increased 3.5-fold (from -6.72 ± 1.73 to -26 ± 4.81 nmol · min-1 · g-1, P < 0.001). Gastrocnemius glutamine synthetase activity fell 48% after denervation (from 475 ± 81 to 248 ± 39 nmol · min-1 · g-1, P < 0.001), but glutaminase activity was not significantly altered (17 nmol · min-1 · g-1). The maximal activity (V(max)) of the unidirectional Na+-dependent glutamine transporter (system Nm) was depressed by 45% from 1,020 ± 104 to 571 ± 9 nmol · min-1 · g-1 (P < 0.01), but the concentration at which transport transport was half maximal (K(m)) was not significantly altered (control 8.1 ± 0.6 mM; denervated 6.52 ± 0.12). Hindlimb denervation resulted in an increase of intramuscular Na+ by 17% and a fall of K+ by 12%, and the resting membrane potential in isolated muscles decreased from -75 ± 10 to -59.5 ± 5.5 mV. Membrane potential of perfused denervated muscle, isolated after acute addition of the Na+ channel blocker tetrodotoxin (TTX, 3 μM), repolarized to -66.4 ± 3.2 mV. In perfused denervated preparations TTX caused an acute recovery of V(max) of unidirectional glutamine transport to 848 ± 75 nmol · min-1 · g-1; K(m) was unaffected. It is likely that the marked reduction in intramuscular glutamine occurring after hindlimb denervation is due to a combination of 1) a fall in the Na+ electrochemical gradient (i.e., the net driving force for intracellular glutamine accretion diminishes), 2) depressed synthesis of glutamine as suggested by the lower activity of glutamine synthetase, and 3) accelerated sarcolemmal glutamine efflux.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume259
Issue number2 22-2
Publication statusPublished - 1 Jan 1990

Keywords

  • Amino acid
  • Cell membrane
  • Injury
  • Trauma

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