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The increases in the intracellular concentrations of inorganic phosphate and hydrogen ion accompanying fatigue of skeletal muscle appear to be the most important metabolic changes associated with the decrease in contractile force. Experiments on chemically skinned single fibers from rabbit psoas muscle with pH ranging between 6 and 7.25 demonstrate that the depression of maximal calcium-activated force by inorganic phosphate correlates nicely with the concentration of the acidic (diprotonated) species. Therefore, in addition to the well-known depressant effect on the contractile machinery of lowering pH per se, any decrease of intracellular pH associated with fatigue further depresses force production by converting more of the total inorganic phosphate within the cell to the inhibitory diprotonated form.
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