Transport of Ca2+ from sarcoplasmic reticulum to mitochondria in rat ventricular myocytes

J Bioenerg Biomembr. 2000 Feb;32(1):97-104. doi: 10.1023/a:1005520714221.


Studies with electron microscopy have shown that sarcoplasmic reticulum (SR) and mitochondria locate close to each other in cardiac muscle cells. We investigated the hypothesis that this proximity results in a transient exposure of mitochondrial Ca2+ uniporter (CaUP) to high concentrations of Ca2+ following Ca2+ release from the SR and thus an influx of Ca2+ into mitochondria. Single ventricular myocytes of rat were skinned by exposing them to a physiological solution containing saponin (0.2 mg/ml). Cytosolic Ca2+ concentration ([Ca2+]c) and mitochondrial Ca2+ concentration ([Ca2+]m) were measured with fura-2 and rhod2, respectively. Application of caffeine (10 mM) induced a concomitant increase in [Ca2+]c and [Ca2+]m. Ruthenium red, at concentrations that block CaUP but not SR release, diminished the caffeine-induced increase in [Ca2+]m but not [Ca2+]c. In the presence of 1 mM BAPTA, a Ca2+ chelator, the caffeine-induced increase in [Ca2+]m was reduced substantially less than [Ca2+]c. Moreover, inhibition of SR Ca2+ pump with two different concentrations of thapsigargin caused an increase in [Ca2+]m, which was related to the rate of [Ca2+]c increase. Finally, electron microscopy showed that sites of junctions between SR and T tubules from which Ca2+ is released, or Ca2+ release units, CRUs, are preferentially located in close proximity to mitochondria. The distance between individual SR Ca2+ release channels (feet or ryanodine receptors) is very short, ranging between approximately 37 and 270 nm. These results are consistent with the idea that there is a preferential coupling of Ca2+ transport from SR to mitochondria in cardiac muscle cells, because of their structural proximity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport
  • Calcium / metabolism*
  • Chelating Agents / pharmacology
  • Egtazic Acid / analogs & derivatives*
  • Egtazic Acid / pharmacology
  • Heart Ventricles
  • Kinetics
  • Male
  • Mitochondria, Heart / drug effects
  • Mitochondria, Heart / metabolism*
  • Mitochondria, Heart / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Sarcoplasmic Reticulum / metabolism*


  • Chelating Agents
  • Egtazic Acid
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Calcium