Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Babcock, D. F., Herrington, J., Goodwin, P. C., Park, Y. B., and Hille, B. (1997). J. Cell Biol. 136, 833-844.
Babcock, D. F., and Hille, B. (1998). Current Opinion Neurobiol. 8, 398-404.
Bers, D. M., Bassani, J.W., and Bassani, R. A. (1993). Cardiovasc. Res. 27, 1772-1777.
Carafoli, E. (1987). Annu. Rev. Biochem. 56, 395-433.
Crompton, M., Sigel, E., Salzmann, M., and Carafoli, E. (1976). Eur. J. Biochem. 69, 429-434.
Fabiato, A. (1983). Amer. J. Physiol. 245, C1-C14.
Fabiato, A. (1988). Methods Enzymol. 157, 378-417.
Gillis, J. M. (1997). J. Muscle Res. Cell Motility 18, 473-483.
Grynkiewicz, G., Poenie, M., and Tsien, R. Y. (1985). J. Biol. Chem. 260, 3440-3450.
Gunter, T. E., Gunter, K. K., Sheu, S-S., and Gavin, C. E. (1994). Amer. J. Physiol. 267, C313-C339.
Hajnóczky, G., Robb-Gaspers, L. D., Seitz, M. B., and Thomas, A. P. (1995). Cell 82, 415-424.
Hajnóczky, G., Csordas, G., and Thomas, A. P. (1998). Frontiers of Mitochondrial Research, 33P.
Hüser, J., Blatter, L. A., and Sheu, S-S. (2000). J. Bioener. Biomembr. 32, 00-00.
Isenberg, G., Han, S., Schiefer, A., and Wendt-Gallitelli, M. F. (1993). Cardiovasc. Res. 27, 1800-1809.
Jou, M-J., Peng, T-I., and Sheu, S-S. (1996). J. Physiol. 497, 299-308.
Miyata, H., Silverman, H. S., Sollott, S. J., Lakatta, E. G., Stern, M. D., and Hansford, R. G. (1991). Amer. Physiol. 261, H1123-H1134.
Neary, P., Steele, D. S., Orchard, C. H., and Smith G. L. (1996). J. Physiol. 497, 7P.
Nieminen, A-L., Dawson, T. L., Gores, G. J., Kawanishi, T., Herman, B., and Lemasters, J. J. (1990). Biochem. Biophys. Res. Commun. 167, 600-606.
Ramesh, V., Sharma, V. K., Sheu, S-S., and Franzini-Armstrong, C. (1985). Ann. N. Y. Acad. Sci. 853, 341-344.
Rizzuto, R., Brini, M., Murgia, M., and Pozzan, T. (1993). Science 262, 744-747.
Rizzuto, R., Bastianutto, C., Brini, M., Murgia, M., and Pozzan, T (1994). J. Cell. Biol. 126, 1183-1194.
Rizzuto, R., Pinton, P., Carrington, W., Fay, F. S., Fogarty, K. E., Lifshitz, L. M., Tuft, R. A., and Pozzan, T (1998). Science, 280, 1763-1766.
Scarpa, A., and Graziotti, P. (1973). J. Gen. Physiol. 62, 756-772.
Sharma, V. K., Colecraft, H. M., Wang, D. X., Levey, A. I., Grigorenko, E. V., Yeh H. H., and Sheu, S-S. (1996). Cir. Res. 79, 86-93.
Sheu, S-S., Sharma, V. K., Ramesh, V., and Franzini-Armstrong, C. (1998). Frontiers of Mitochondrial Research 84P.
Sommer, J. R., and Johnson, E., A. (1979). In Handbook of Physiology: The Cardiovascular System (Berne, R. M. ed.), Vol. I, The Heart, American Physiological Society, Washington, DC, pp. 113-186.
Thayer, S. A., and Miller, R. J. (1990). J. Physiol. 425, 85-116.
Trollinger, D. R., Cascio, W. E., and Lemasters, J. J. (1997). Biochem. Biophys. Res. Commun. 236, 738-742.
Tsien, R. Y., and Bacskai, B. J. (1995). In Handbook of Biological Confocal Microscopy (Pawley, J. B. ed.), Plenum Press, New York, pp. 459-478.
Vasington, F. D., Gazzotti, P., Tiozzo, R., and Carafoli, E. (1972). Biochim. Biophys. Acta 256, 43-54.
Wendt-Gallitelli, M-F, and Isenberg, G. (1991). J. Physiol. 435, 349-372.
Weber, A., and Herz, R. (1968). J. Gen. Physiol. 52, 750-759.
Zhou, Z., Matlib, M. A., and Bers, D. M. (1998). J. Physiol. 507, 379-403.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sharma, V.K., Ramesh, V., Franzini-Armstrong, C. et al. Transport of Ca2+ from Sarcoplasmic Reticulum to Mitochondria in Rat Ventricular Myocytes. J Bioenerg Biomembr 32, 97–104 (2000). https://doi.org/10.1023/A:1005520714221
Issue Date:
DOI: https://doi.org/10.1023/A:1005520714221