Effects of short-term hypoxia on skeletal musclecalcium handling

Abstract: Introduction: Calcium is the trigger for muscle contraction and strict control ofintracellular calcium handling is fundamental for muscle function. Imbalances in theintracellular concentration of calcium caused by disturbances in the calcium ion pumps orcalcium channels may be responsible for different types of muscle disorders as myopathies.The pathogenesis of myopathy is unknown, but it has been hypothesized that hypoxia mightbe the trigger of a cascade leading to muscle weakness. Hypoxia is known to induce calciumhandling alterations in many cell types, but effects of hypoxia on calcium handling in skeletalmuscle is still uninvestigated. Aim: To investigate if acute hypoxia affects calcium release and re-uptake in dissociatedmuscle fibres after intermittent tetanic stimulation, with the purpose to increase theknowledge of the role of hypoxia in diseases causing muscle weakness. Method: Single fibres were dissociated from the flexor digitorum brevis taken from mice.These were cultured overnight and then exposed to hypoxia for 30 minutes. Alterations in thefree cytoplasmic calcium ion concentration transients were measured before and after a seriesof 300 intermittent contractions at 70 Hz using fluo-3, which is a fluorescence indicator ofintracellular calcium. Result: Acute hypoxia affected calcium handling in skeletal muscle fibres. Decay of thetetanic free cytoplasmic calcium ion concentration transient was significantly slower inhypoxic compared to control fibres. Resting free cytoplasmic calcium ion concentration andtetanic free cytoplasmic calcium ion concentration seemed to increase prior to fatigue andaccelerate the development of fatigue. Conclusion: Calcium handling alterations induced by acute hypoxia in skeletal musclefibres may have resulted from acidosis and metabolite alterations. Further studies need to beperformed to draw firm conclusions due to limited samples in this study.