PMID: 8600972Mar 15, 1996Paper

Mechanism of thermal uncoupling of Ca2+-ATPase of sarcoplasmic reticulum as revealed by thapsigargin stabilization

Biochimica Et Biophysica Acta
G A Davidson, M C Berman

Abstract

Thermal uncoupling of the Ca2+ pump of skeletal muscle sarcoplasmic reticulum is specifically blocked by binding of Ca2+ to the high affinity sites, having identical characteristics to the Ca2+ transport sites (Berman, M.C., McIntosh, D.B. and Kench, J.E. (1977) J. Biol. Chem. 252, 994-1001). The present study has investigated the nature of the decreased net Ca2+ transport in the uncoupling process. Ca2+ uptake in the presence and absence of oxalate, Ca2+ retention following passive Ca2+ loading and Ca2+-dependent ATPase activity were inactivated at pH 7.0 and 37 degrees C, with rate constants of 0.12, 0.047, 0.053 and 0.001 min-1, respectively. Activation energies were in the range 72-76 kcal/mol, indicating a common irreversible protein conformational transition. A thermodynamic analysis of parallel or consecutive inactivation pathways revealed that loss of Ca2+ transfer and ATPase activity occurred on the same pump unit, making the existence of a predominant uncoupled intermediate unlikely. Decreased passive Ca2+ loading, an index of the number of intact vesicles, correlated with decreased active uptake in the absence of oxalate, indicating increased vesicle permeability. Thapsigargin, at a 1:1 stoichiometry, stabilised the ...Continue Reading

References

Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·M Hartl, K Bister

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Citations

Sep 13, 2008·Clinical and Experimental Pharmacology & Physiology·Chris van der PoelD George Stephenson
Jun 28, 2014·Biomolecules·Ernesto A Roman, F Luis González Flecha
Jan 12, 2008·Archives of Biochemistry and Biophysics·Diego I CattoniJosé M Argüello
Nov 23, 2006·The International Journal of Biochemistry & Cell Biology·Carla F FelixHelena M Scofano
Feb 21, 2006·Physical Review Letters·Man-Duen Choi, David W Kribs
Oct 17, 2008·Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquée, Nutrition Et Métabolisme·A Russell TuplingMinghua Fu
Mar 9, 2007·American Journal of Physiology. Cell Physiology·C van der Poel, D G Stephenson
May 13, 2006·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·T A DuhamelH J Green
Sep 10, 2002·American Journal of Physiology. Endocrinology and Metabolism·J D SchertzerA R Tupling
Apr 1, 2014·Temperature : Multidisciplinary Biomedical Journal·Sandra I Rosado MontillaJoshua T Selsby
Oct 30, 2020·Journal of Applied Physiology·James J McCormickGlen P Kenny

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