Use of ruthenium red as an inhibitor of mitochondrial Ca(2+) uptake in single rat cardiomyocytes.
With the current resurgence of interest in the role of mitochondrial [Ca(2+)] in energy production and cellular Ca(2+) signalling, ruthenium red (RR) is being increasingly used as an inhibitor of mitochondrial Ca(2+) uptake. In the present study, the effects of RR on cell and mitochondrial [Ca(2+)], and on cell contractility were determined in isolated rat ventricular myocytes subjected to adrenergic and electrical stimulation. At low concentrations, 0-1 microM, RR inhibited mitochondrial Ca(2+) uptake but this was a secondary effect due to a reduced total intracellular [Ca(2+)], a conclusion supported by the ability of RR to inhibit cell shortening. 5 microM RR completely inhibited cell contraction, whereas higher concentrations, 10-25 microM, induced spontaneous Ca(2+) oscillations and contractile waves. These results indicate that great care must be taken when using RR in intact cells, and in interpreting any effects as resulting from a primary inhibition of mitochondrial Ca(2+) uptake.
Griffiths
E J
EJ
Bristol Heart Institute, Department of Cardiac Surgery, Level 7, Bristol Royal Infirmary, University of Bristol, BS2 8HW, Bristol, UK. elinor.griffiths@bristol.ac.uk
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000494:pharmacology*; D012508:Sarcolemma / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013268:Stimulation, Chemical; D019284:Thapsigargin / Q000494:pharmacology
D012430:Ruthenium Red; D019284:Thapsigargin; D012964:Sodium; D002118:Calcium; D009638:Norepinephrine