Transport of Ca2+ from Sarcoplasmic Reticulum to Mitochondria in Rat Ventricular Myocytes
- Cite this article as:
- Sharma, V.K., Ramesh, V., Franzini-Armstrong, C. et al. J Bioenerg Biomembr (2000) 32: 97. doi:10.1023/A:1005520714221
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Studies with electron microscopy have shown that sarcoplasmic reticulum (SR) andmitochondria locate close to each other in cardiac muscle cells. We investigated the hypothesis thatthis proximity results in a transient exposure of mitochondrial Ca2+ uniporter (CaUP) to highconcentrations 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 aphysiological 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 thecaffeine-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 anincrease in [Ca2+]m, which was related to the rate of [Ca2+]c increase. Finally, electronmicroscopy 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) isvery short, ranging between approximately 37 and 270 nm. These results are consistent withthe idea that there is a preferential coupling of Ca2+ transport from SR to mitochondria incardiac muscle cells, because of their structural proximity.