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Inhibitors of SERCA and mitochondrial Ca-uniporter decrease velocity of calcium waves in rat cardiomyocytes

G Landgraf1, F N Gellerich, M H P Wussling

  • 1Julius Bernstein Institute of Physiology, Martin Luther University Halle-Wittenberg, Halle, Germany.

Molecular and Cellular Biochemistry
|February 24, 2004
PubMed

Insights

This study reveals how calcium overload affects spontaneous calcium waves in rat heart cells. Inhibiting calcium uptake by the sarcoplasmic reticulum (SR) and mitochondria significantly slows these waves, impacting cell signaling.

Area of Science:

  • Cardiology
  • Cell Physiology
  • Biophysics

Background:

  • Spontaneous calcium waves are crucial for cardiomyocyte function.
  • Understanding the regulation of intracellular calcium is vital for cardiac health.

Purpose of the Study:

  • To investigate the impact of sarcoplasmic reticulum (SR) and mitochondrial calcium uptake on spontaneous calcium wave propagation in isolated rat cardiomyocytes.
  • To quantify the role of SERCA in regulating calcium wave dynamics.

Main Methods:

  • Confocal laser scanning microscopy was used to visualize calcium waves.
  • The fluorescent calcium indicator fluo-4 AM was employed.
  • Pharmacological agents, including thapsigargin (SERCA inhibitor) and RU 360 (mitochondrial calcium uptake inhibitor), were utilized.

Main Results:

  • Calcium wave propagation velocity increased with calcium overload.
  • Inhibition of SR calcium uptake by thapsigargin significantly reduced wave speed, with flux control coefficients increasing with calcium overload.
  • Inhibition of mitochondrial calcium uptake by RU 360 also decreased calcium wave velocity.
  • Spontaneous calcium waves were abolished at high thapsigargin concentrations (above 20 nM).

Conclusions:

  • Intracellular calcium signaling is dependent on both SR lumenal and cytosolic calcium concentrations.
  • Reduced calcium uptake by SR and mitochondria affects the propagation of spontaneous calcium waves, likely by modulating ryanodine receptor activity.

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