ISSN:
1573-6881
Keywords:
Calcium uniporter inhibitors
;
mitochondria
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Physics
Notes:
Abstract The recent finding that the inhibition of Ca2+-stimulated respiration by ruthenium red is mainlydue to a binuclear ruthenium complex (Ru360) present in the commercial samples of the classicalinhibitor ruthenium red (Ying et. al., 1991), showed that this complex is the more potent andspecific inhibitor of the mitochondrial calcium uniporter. This work was aimed to provideinsights into the mechanism by which Ru360 and other ruthenium-related compounds inhibitscalcium uptake. Ruthenium red and a synthesized analog (Rrphen) were compared with Ru360.The inhibition by this binuclear complex was noncompetitive, with a K i of 9.89 nM. Thenumber of specific binding sites for Ru360 was 6.2 pmol/mg protein. Ruthenium red and Ru360were mutually exclusive inhibitors. Bound La3+ was not displaced by Ru360. Rrphen was theleast effective for inhibiting calcium uptake. The results support the notion of a specific bindingsite in the uniporter for the polycationic complexes and a negative charged region from thephospholipids in the membrane, closely associated with the uniporter inhibitor-binding site.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1005464927366
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