The effects of intracellular injections of phosphate on intracellular calcium and force in single fibres of mouse skeletal muscle.

Intracellular inorganic phosphate increases during muscle fatigue and may be responsible for certain of the changes in muscle function observed in fatigue. To test this hypothesis inorganic phosphate was micro-injected in single mouse muscle fibres which were also injected with indo-1 to measure intracellular Ca2+. Following phosphate injection, intracellular Ca2+, both at rest and during tetani, was reduced as was tetanic force. The rate at which the sarcoplasmic reticulum (SR) pumped Ca2+ out of the myoplasm was accelerated following phosphate injection. Intracellular Ca2+ and force recovered over 1-h. The changes in maximum Ca2+-activated force and Ca2+ sensitivity which would be expected if the phosphate remained in the myoplasm were largely absent. The most likely interpretation is that inorganic phosphate enters the SR where it precipitates with Ca2+ and thereby reduced release of Ca2+ from the SR and accelerated the rate of uptake of Ca2+ by the pump. The 1-h recovery may represent the entry of additional Ca2+ into the cell to reestablish the normal gradient of Ca2+ across the sarcolemma.