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The role of the myoplasmic free Mg2+ concentration (Mg2+i) in fatigue was studied in intact single fibres isolated from mouse skeletal muscle. Fatigue was produced by repeated tetanic stimulation. The fluorescent Mg2+ indicator furaptra was pressure injected into fibres. In vivo calibrations were performed to convert fluorescence signals into Mg2+i. 2. Mg2+i at rest was 0.78 +/- 0.05 mM (mean +/- S.E.M., n = 14). An increase of the extracellular Mg2+ from 0.5 to 20 mM resulted in a small elevation of Mg2+i (86 microM in 5 min). Removal of extracellular Na+ did not affect Mg2+i. An intracellular alkanization of about 0.6 pH units gave a Mg2+i reduction of 65 microM. 3. During fatiguing stimulation Mg2+i initially remained almost constant and it then suddenly started to rise towards the end of the stimulation period. The onset of the Mg2+i rise was always followed by a rapid tension decline. In fatigue Mg2+i was approximately twice as high as at rest. 4. Fibres were injected with MgCl2 to study if the rise in Mg2+i could explain the tension decline in fatigue. An elevation of Mg2+i was accompanied by a tension reduction but the Mg2+i for a given tension was generally much higher in rested fibres injected with MgCl2 than in fatigued fibres. Thus the rise in Mg2+i as such cannot explain the tension reduction in fatigue. 5. Injection of MgCl2 was also used to assess the intracellular Mg2+ buffering. The mean Mg2+ buffer power (i.e. the ratio of the change in Mg2+i to the amount of Mg2+ added) was 0.62. 6. ATP is the quantitatively most important binding site for Mg2+ at rest and ATP breakdown is then a likely source of the Mg2+i increase in fatigue. The role of ATP breakdown in the increase of Mg2+i was studied with metabolic inhibition: fibres were exposed to iodoacetic acid to inhibit glycolysis and cyanide to inhibit oxidative phosphorylation. The pattern during metabolic inhibition was similar to that observed during fatigue. After remaining almost constant during a lengthy period, Mg2+i rose rapidly and this rise preceded a period of rapid tension decline. The fibres thereafter went into rigor and Mg2+i stabilized at an elevated level; the mean Mg2+i increase in rigor was 1.30 mM. 7. We have used modelling to determine the likely change in the intracellular ATP concentration (ATPi) for the observed changes in Mg2+i.(ABSTRACT TRUNCATED AT 400 WORDS)
Westerblad et al. (Wed,) studied this question.