Use of ruthenium red as an inhibitor of mitochondrial Ca2+ uptake in single rat cardiomyocytes

With the current resurgence of interest in the role of mitochondrial [Ca2+] in energy production and cellular Ca2+ signalling, ruthenium red (RR) is b eing increasingly used as an inhibitor of mitochondrial Ca2+ uptake. In the present study, the effects of RR on cell and mitochondrial [Ca2+], and on cell contractility were determined in isolated rat ventricular myocytes sub jected to adrenergic and electrical stimulation. At low concentrations, 0-1 muM, RR inhibited mitochondrial Ca2+ uptake but this was a secondary effec t due to a reduced total intracellular [Ca2+], a conclusion supported by th e ability of RR to inhibit cell shortening. 5 muM RR completely inhibited c ell contraction, whereas higher concentrations, 10-25 muM, induced spontane ous Ca2+ oscillations and contractile waves. These results indicate that gr eat care must be taken when using RR in intact cells, and in interpreting a ny effects as resulting from a primary inhibition of mitochondrial Ca2+ upt ake. (C) 2000 Federation of European Biochemical Societies. Published by El sevier Science B.V. All rights reserved.