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Calcium-induced inactivation of calcium release from the sarcoplasmic reticulum of skeletal muscle


Calcium-induced inactivation of calcium release from the sarcoplasmic reticulum of skeletal muscle



Pflugers Archiv: European Journal of Physiology 419(2): 166-176



ISSN/ISBN: 0031-6768

PMID: 1961687

DOI: 10.1007/bf00373003

The ability of myofilament space Ca2+ to modulate Ca2+ release from the sarcoplasmic reticulum (SR) of skeletal muscle was investigated. Single fibers of the frog Rana pipiens belindieri were manually skinned (sarcolemma removed). Following a standard load and pre-incubation in varying myoplasmic Ca2+ concentrations, SR Ca2+ release was initiated by caffeine. Ca2+ release rates were calculated from the changes in absorbance of a Ca2+ sensitive dye, antipyrylazo III. An apparent dissociation constant (Kd) for dye-Ca2+ binding of 8000 microM 2 was determined by comparing the buffering action of the dye with that of ethylenebis(oxonitrilo)tetraacetate (EGTA) using the contractile proteins of the skinned fiber as a measure of free Ca2+. This value for Kd was used in the calculation of Ca2+ release rates. As the myoplasmic space Ca2+ was increased from pCa 7.4, Ca2+ release rates declined sharply such that at pCa 6.9 the calculated release rate was 72 +/- 3% (mean +/- SEM) of control (pCa 8.4). Further increases in myoplasmic Ca2+ from pCa 6.9 to pCa 6.1 did not result in a further decline in release rate. The effect of a decreased driving force on Ca2+ ions was investigated to determine whether it could account for the change in release rates observed. At pCa 6.9, where the greatest degree of inactivation occurred, the measured effects of a change in driving force could account for at most 40% of the observed inactivation. Varying concentrations of Ba2+ and Sr2+ in the myofilament space had no inactivating effect on the SR Ca2+ release rates. The ability of myofilament Ca2+ to inhibit SR Ca2+ release at concentrations normally encountered during muscle activation suggests a role for released Ca2+ as a modulator of the SR Ca2+ channel.

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Accession: 039442934

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