Sphingosylphosphocholine (SPC) modulates Ca2+ release from isolated cardiac sarcoplasmic reticulum membranes; 50 ƁM SPC induces the release of 70Ő80% of the accumulated calcium. SPC releases calcium from cardiac sarcoplasmic reticulum through the ryanodine receptor, since the release is inhibited by the ryanodine receptor channel antagonists ryanodine, Ruthenium Red and sphingosine. In intact cardiac myocytes, even in the absence of extracellular calcium, SPC causes a rise in diastolic Ca2+, which is greatly reduced when the sarcoplasmic reticulum is depleted of Ca2+ by prior thapsigargin treatment. SPC action on the ryanodine receptor is Ca2+-dependent. SPC shifts to the left the Ca2+-dependence of [3H]ryanodine binding, but only at high pCa values, suggesting that SPC might increase the sensitivity to calcium of the Ca2+-induced Ca2+-release mechanism. At high calcium concentrations (pCa 4.0 or lower), where [3H]ryanodine binding is maximally stimulated, no effect of SPC is observed. We conclude that SPC releases calcium from cardiac sarcoplasmic reticulum membranes by activating the ryanodine receptor and possibly another intracellular Ca2+-release channel, the sphingolipid Ca2+-release-mediating protein of endoplasmic reticulum (SCaMPER) [Mao, Kim, Almenoff, Rudner, Kearney and Kindman (1996) Proc. Natl. Acad. Sci. U.S.A 93, 1993Ő1996], which we have identified for the first time in cardiac tissue.
Sphingosylphosphocholine modulates the ryanodine receptor/calcium-release channel of cardiac sarcoplasmic reticulum membranes
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Romeo BETTO, Alessandra TERESI, Federica TURCATO, Giovanni SALVIATI, Roger A. SABBADINI, Kevin KROWN, Chris C. GLEMBOTSKI, L. Allen KINDMAN, Christine DETTBARN, Yann PEREON, Kenji YASUI, Philip T. PALADE; Sphingosylphosphocholine modulates the ryanodine receptor/calcium-release channel of cardiac sarcoplasmic reticulum membranes. Biochem J 15 February 1997; 322 (1): 327–333. doi: https://doi.org/10.1042/bj3220327
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