Abstract: | The effects of Pi onsarcoplasmic reticulum (SR) Ca2+ regulation were studied inmechanically skinned rat skeletal muscle fibers. Brief application ofcaffeine was used to assess the SR Ca2+ content, andchanges in concentration of Ca2+(Ca2+]) within the cytosol were detected withfura 2 fluorescence. Introduction of Pi (1-40 mM)induced a concentration-dependent Ca2+ efflux from the SR.In solutions lacking creatine phosphate (CP), the amplitude of thePi-induced Ca2+ transient approximatelydoubled. A similar potentiation of Pi-induced Ca2+ release occurred after inhibition of creatine kinase(CK) with 2,4-dinitrofluorobenzene. In the presence of ruthenium red or ryanodine, caffeine-induced Ca2+ release was almostabolished, whereas Pi-induced Ca2+ release wasunaffected. However, introduction of the SR Ca2+ ATPaseinhibitor cyclopiazonic acid effectively abolishedPi-induced Ca2+ release. These data suggestthat Pi induces Ca2+ release from the SR byreversal of the SR Ca2+ pump but not via the SRCa2+ channel under these conditions. If this occurs inintact skeletal muscle during fatigue, activation of a Ca2+efflux pathway by Pi may contribute to the reporteddecrease in net Ca2+ uptake and increase in restingCa2+]. |