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Impaired calcium uptake by cardiac sarcoplasmic reticulum and its underlying mechanism in endotoxin shock

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Abstract

Effects of endotoxin administration on the ATP-dependent Ca2+ uptake by canine cardiac sarcoplasmic reticulum (SR) were investigated. Results obtained 4 h after endotoxin administration show that ATP-dependent Ca2+ uptake by cardiac SR was decreased by 27–43% (p < 0.05). Kinetic analysis indicates that the Vmax values for Ca2+ and for ATP were significantly decreased while the S0.5 and the Hill coefficient values were not affected during endotoxin shock. Magnesium (1–5 mM) stimulated while vanadate (25–50 μM) inhibited the ATP-dependent Ca2+ uptake, but the Mg2+-stimulated and the vanadate-inhibited activities remained significantly lower in the endotoxin-treated animals. Phosphorylation of SR by the exogenously added catalytic subunit of the cAMP-dependent protein kinase or by the addition of calmodulin stimulated the ATP-dependent Ca2+ uptake activities both in the control and endotoxin-injected dogs. However, the phosphorylation-stimulated activities remained significantly lower in the endotoxin-injected dogs. Dephosphorylation of SR decreased the ATP-dependent Ca2+ uptake, but the half-time required for the maximal dephosphorylation was reduced by 31% (p < 0.05) 4 h post-endotoxin. These data indicate that endotoxin administration impairs the ATP-dependent Ca2+ uptake in canine cardiac SR and the endotoxininduced impairment in the SR calcium transport is associated with a mechanism involving a defective phosphorylation and an accelerated dephosphorylation of SR membrane protein. Since ATP-dependent Ca2+ uptake by cardiac SR plays an important role in the regulation of the homeostatic levels of the contractile calcium, our findings may provide a biochemical explanation for myocardial dysfunction that occurs during endotoxin shock.

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  1. Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, 63104, St. Louis, MO, USA

    Li-Ling Wu & Maw-Shung Liu

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  1. Li-Ling Wu
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  2. Maw-Shung Liu
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Wu, LL., Liu, MS. Impaired calcium uptake by cardiac sarcoplasmic reticulum and its underlying mechanism in endotoxin shock. Mol Cell Biochem 108, 9–17 (1991). https://doi.org/10.1007/BF00239537

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  • DOI: https://doi.org/10.1007/BF00239537

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