Metabolite patterns related to exhaustion, recovery and transformation of chronically stimulated rabbit fast-twitch muscle

Abstract

Rabbit fast-twitch tibialis anterior muscle was subjected to chronic low-frequency stimulation (10 Hz, 24 h/day). Measurements of the time course of changes in the concentration of metabolites of energy metabolism were performed in order to test the hypothesis whether or not alterations in the metabolite profile might represent possible signals for triggering muscle fibre type transformation. Most of the investigated metabolites displayed triphasic changes in response to persistently increased contractile activity. During the first 15 min of stimulation, drastic reductions were observed for adenosine triphoshate (ATP, 56%), phosphocreatine (PCr, 60%) and glycogen (76%), as well as 3- to 4-fold and 10-fold increases for glucose and lactate, respectively. This early metabolic perturbance coincided with a rapid reduction of isometric force. The next phase, extending to 4 days of stimulation, was characterized by a nearly complete recovery of ATP and PCr, and an overshoot in glycogen. The first signs of metabolic recovery were already detectable in 60-min-stimulated muscle when isometric force was still markedly depressed. These results demonstrated an impressive capability of the muscle to recover with ongoing stimulation from an initial, dramatic disturbance in energy metabolism. During the final phase, extending to 50 days, the metabolite profile approached that of a slow-twitch muscle with moderate reductions in total adenine nucleotides, ATP, total creatine, PCr and glycogen. A conspicuous result was the finding that, contrary to the recovery of most metabolites, the ratio of ATP to the product of free adenosine diphosphate and resting free inorganic phosphate was persistently depressed with ongoing stimulation. Therefore, the depressed phosphorylation potential of the adenylate system may be an important signal triggering muscle fibre type transformation.