What is the clinical evidence from this study?

Intervention: Ouabain. Primary outcome: Cytosolic Ca2+ concentration and sarcoplasmic reticulum Ca2+ store loading.

What question did this study set out to answer?

To simulate and evaluate the specific pathways through which ouabain influences intracellular calcium trafficking, store dynamics, and microdomain signaling.

August 2, 2007AJP Renal Physiology

Ouabain modulation of cellular calcium stores and signaling

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Key result

Mathematical modeling predicts that ouabain enhances agonist-evoked cytosolic Ca2+ transients by inhibiting alpha2-isoform Na+ transport and increasing Ca2+ loading into sarcoplasmic reticulum stores.

Population

Mathematical model of Ca2+ trafficking in cytoplasm and subplasmalemmal microdomains

Design

Preclinical

Authors

AEAurélie EdwardsBoston University TPThomas L. PalloneUniversity of Maryland, Baltimore

Discussion

Member takes

Implication

No immediate clinical implications; leaves open translation of ouabain-Ca2+ modeling to human physiology.

Key Points

To simulate and evaluate the specific pathways through which ouabain influences intracellular calcium trafficking, store dynamics, and microdomain signaling.
Constructed a mathematical model of calcium trafficking encompassing both the bulk cytoplasm and subplasmalemmal microdomains.
Simulated transport inhibition of Na+-K+-ATPase alpha1- and alpha2-isoforms alongside inositol trisphosphate (IP3) production and IP3 receptor sensitization.
Inhibition of Na+-K+-ATPase favors sarcoplasmic reticulum calcium loading, whereas Src-mediated IP3 production and IP3 receptor sensitization drive store depletion.
Alpha2-isoform inhibition causes a peak-and-plateau pattern of cytosolic calcium elevation without significantly altering cytosolic sodium levels, whereas alpha1-isoform inhibition produces a monophasic elevation.
Spatial localization of IP3 production within microdomains critically governs compartmental calcium shifts and enhances agonist-evoked calcium transients.

Structured PICO

Population

Mathematical model of Ca2+ trafficking in cytoplasm and subplasmalemmal microdomains

Exposure

Simulated ouabain effects (inhibition of active transport by Na+-K+-ATPase alpha1- and alpha2-isoforms, activation of IP3 production, and increased IP3R conductance)

Outcome

Changes in compartmental Ca2+ concentrations and cytosolic Ca2+ concentration ([Ca2+](cyt)) elevation patternssurrogate

Mathematical modeling supports the hypothesis that ouabain enhances agonist-evoked cytosolic Ca2+ transients primarily by inhibiting alpha2-isoform Na+ transport and increasing Ca2+ loading into sarcoplasmic reticulum stores.

Cite This Study

Edwards et al. (2007) studied this question. Ouabain was evaluated on Cytosolic Ca2+ concentration and sarcoplasmic reticulum Ca2+ store loading. Mathematical modeling predicts that ouabain enhances agonist-evoked cytosolic Ca2+ transients by inhibiting alpha2-isoform Na+ transport and increasing Ca2+ loading into sarcoplasmic reticulum stores.

synapsesocial.com/papers/6a99f068e87681eadfde8f8d https://doi.org/10.1152/ajprenal.00251.2007

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Ouabain modulation of cellular calcium stores and signaling

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Ouabain modulation of cellular calcium stores and signaling

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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