KB-R7943 Inhibits the Mitochondrial Ca²⁺ Uniporter but Not Na⁺–Ca²⁺ Exchanger in Cardiomyocyte-Derived H9c2 Cells

Abstract

The effect of KB-R7943, an inhibitor of the plasmalemmal Na⁺–Ca²⁺ exchanger, on mitochondrial Ca²⁺ transporters was examined with membrane-permeabilized cardiomyocyte-derived H9c2 cells expressing the fluorescent Ca²⁺ indicator, yellow cameleon 3.1, in the mitochondria. KB-R7943, as well as ruthenium red, inhibited the rise in mitochondrial Ca²⁺ on increasing the extramitochondrial Ca²⁺ concentration from 0 nM to 300 nM. CGP-37157, but not KB-R7943, inhibited the decline in mitochondrial Ca²⁺on return to Ca²⁺ free extramitochondrial solution. These results indicated that KB-R7943 has inhibitory effects on the mitochondrial Ca²⁺ uniporter, but not on the mitochondrial Na⁺–Ca²⁺ exchanger.

Graphical Abstract