EFFECTS OF TETRODOTOXIN-INDUCED NEURAL INACTIVATION ON SINGLE MUSCLE-FIBER METABOLIC ENZYMES

Selected enzymes were measured in mixed-fiber bundles and individual f ibers from rat plantaris (PL) and soleus (Sol) muscles that had underg one either 2 wk of tetrodotoxin (TTX) inactivation of the sciatic nerv e, a sham operation, or were contralateral to the TTX limb. TTX disuse caused severe wasting of PL (46%) and Sol (26%) muscles and of single fibers (50% and 40%, respectively). TTX PL and Sol also had reduced ( 50%) glycogen content. In TTX, PL, and Sol macro samples and single fi bers, the activities (mol.h(-1.)kg dry wt(-1)) of hexokinase, glycogen phosphorylase, and lactate dehydrogenase were higher, lower, and unch anged, respectively, compared with controls. Single-fiber data showed that these changes occurred in all fibers. In TTX PL macro samples, ac tivities of glycerol-3-phosphate dehydrogenase (GPDH), pyruvate kinase (PK), malate dehydrogenase (MDH), citrate synthase (CS), beta-hydroxy acyl-CoA dehydrogenase (BOAC), and thiolase were, or tended to be, low er. Single-fiber data showed a disappearance of high-oxidative moderat e glycolytic fibers (i.e., usually fast-twitch oxidative in control) a nd the appearance of more fibers with a metabolic enzyme profile appro aching that of control slow-oxidative fibers. In TTX Sol macro samples , GPDH and PK tended to be higher, and thiolase, BOAC, CS, and MDH low er. Single-fiber data corroborated these findings and suggested the ap pearance of fast fibers with downregulated oxidative enzyme profiles. Our results suggest that neuromuscular activity is a major, but not th e sole, determinant of the size and metabolic heterogeneity that exist s in muscle cells.