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Am J Physiol Cell Physiol 281: C418-C429, 2001;
0363-6143/01 $5.00
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Vol. 281, Issue 2, C418-C429, August 2001

Mechanisms of reduced SR Ca2+ release induced by inorganic phosphate in rat skeletal muscle fibers

Adrian M. Duke and Derek S. Steele

School of Biology, University of Leeds, Leeds LS2 9JT, United Kingdom

The effects of inorganic phosphate (Pi) on Ca2+ release from the sarcoplasmic reticulum (SR) were studied in mechanically skinned rat skeletal muscle fibers. Application of caffeine or T-tubule depolarization was used to induce Ca2+ release from the SR, which was detected using fura 2 fluorescence. Addition of Pi (1-40 mM) caused a reversible and concentration-dependent reduction in the caffeine-induced Ca2+ transient. This effect was apparent at low Pi concentration (<5 mM), which did not result in detectable precipitation of calcium phosphate within the SR. The inhibitory effect of Pi exhibited a marked dependence on free Mg2+ concentration. At 0.5 mM free Mg2+, 5 mM Pi reduced the caffeine-induced transient by 25.1 ± 4.1% (n = 13). However, at 1.5 mM free Mg2+, 5 mM Pi reduced the amplitude of caffeine-induced Ca2+ transients by 68.9 ± 3.1% (n = 10). Depolarization-induced SR Ca2+ release was similarly affected. These effects of Pi may be important in skeletal muscle fatigue, if an inhibitory action of Pi on SR Ca2+ release is augmented by the rise in cytosolic Mg2+ concentration, which accompanies ATP breakdown.

calcium; magnesium; sarcoplasmic reticulum; fatigue


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