title: Mechanisms of reduced SR Ca(2+) release induced by inorganic phosphate in rat skeletal muscle fibers.
abstract: The effects of inorganic phosphate (P(i)) on Ca(2+) 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 Ca(2+) release from the SR, which was detected using fura 2 fluorescence. Addition of P(i) (1-40 mM) caused a reversible and concentration-dependent reduction in the caffeine-induced Ca(2+) transient. This effect was apparent at low P(i) concentration (<5 mM), which did not result in detectable precipitation of calcium phosphate within the SR. The inhibitory effect of P(i) exhibited a marked dependence on free Mg(2+) concentration. At 0.5 mM free Mg(2+), 5 mM P(i) reduced the caffeine-induced transient by 25.1 +/- 4.1% (n = 13). However, at 1.5 mM free Mg(2+), 5 mM P(i) reduced the amplitude of caffeine-induced Ca(2+) transients by 68.9 +/- 3.1% (n = 10). Depolarization-induced SR Ca(2+) release was similarly affected. These effects of P(i) may be important in skeletal muscle fatigue, if an inhibitory action of P(i) on SR Ca(2+) release is augmented by the rise in cytosolic Mg(2+) concentration, which accompanies ATP breakdown.
authors.affiliation: School of Biology, University of Leeds, Leeds LS2 9JT, United Kingdom.
authors.forename: A M
authors.initials: AM
authors.lastname: Duke
authors.forename: D S
authors.initials: DS
authors.lastname: Steele
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002130:Calcium Phosphates / Q000378:metabolism; D011232:Chemical Precipitation; D004056:Differential Threshold; D004338:Drug Combinations; D004594:Electrophysiology; D008274:Magnesium / Q000494:pharmacology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D010070:Oxalates / Q000494:pharmacology; D010710:Phosphates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002130:Calcium Phosphates; D004338:Drug Combinations; D010070:Oxalates; D010710:Phosphates; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; D002110:Caffeine; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; D008274:Magnesium; C485829:calcium phosphate, dibasic, anhydrous; D002118:Calcium