Glutamine synthetase (GS) is a glucocorticoid-inducible enzyme that has a key role for glutamine synthesis in muscle. We hypothesized that the glucocorticoid induction of GS could be altered in aged rats, because alterations in the responsiveness of some genes to glucocorticoids were reported in aging. We compared the glucocorticoid-induced GS in fast-twitch and slow-twitch skeletal muscles (tibialis anterior and soleus, respectively) and heart from adult (age 6-8 mo) and aged (age 22 mo) female rats. All animals received dexamethasone (Dex) in their drinking water (0.77 +/- 0.10 and 0.80 +/- 0.08 mg/day per adult and aged rat, respectively) for 5 days. Dex caused an increase in both GS activity and GS mRNA in fast-twitch and slow-twitch skeletal muscles from adult and aged rats. In contrast, Dex increased GS activity in heart of adult rats, without any concomitant change in GS mRNA levels. Furthermore, Dex did not affect GS activity in aged heart. Thus the responsiveness of GS to an excess of glucocorticoids is preserved in skeletal muscle but not in heart from aged animals.

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Metabolic events with spontaneous malignant hyperthermia crisis in an anaesthetized pigPurpose: To analyze metabolic changes associated with a fulminant malignant hyperthermia (MH) crisis developed spontaneously in an MH susceptible pig which was part of 12 pigs undergoing metabohc investigation (s~x MH susceptible and six controls) and had been anaesthetized with a non-triggering agent (pentobarbitone). Methods: The pig was placed in a cradle and then inserted into a 4.7 T magnet bore. The semi-membranosus muscle was submitted to three repetitive stimulataon-recovery sessions. 31-P magnetic resonance spectra and mechanical data were recorded. Results: The pig developed a non-rigid MH crisis during recovery from the second set of experiments. Although no mechanical work was performed, dramatic metabolic changes were noted. Twitch tension decreased progressively reaching zero while mouth temperature continuously increased to 44.5~ Phosphocreatine (PCr) consumption was coupled to Pi accumulation. Also, a marked intracellular acidosis and a large accumulation of phosphomonoesters (PME) were observed, probably as a result of massive glycolysis activation. Interestingly, ATP level remained constant. Conclusion: These irreversible mechanisms may constitute a metabolic dead-end coupling calcium pumping ATP-consuming processes and ATP synthesis through PCr breakdown and anaerobic glycolysis. They do not differ from metabolic changes previously reported in rigid for'ms of MH crisis.