KB-R7943 inhibits Na+-dependent Mg2+ efflux in rat ventricular myocytes
Tóm tắt
Na+-dependent Mg2+ efflux activity was studied with the fluorescent Mg2+ indicator furaptra in the presence of various potential antagonists known to inhibit other transporters and channels. Among the compounds tested, KB-R7943, an inhibitor of Na+/Ca2+ exchange, most potently inhibited the Na+/Mg2+ exchange with half inhibitory concentrations (IC50) of 21 μM (25°C) and 16 μM (35°C). These IC50 values were a factor of three to four lower than those of imipramine, a widely used inhibitor of Na+/Mg2+ exchange. Apart from the inhibitory effect on Na+/Mg2+ exchange, relatively high concentrations of KB-R7943 (100 μM at 25°C and ≥20 μM at 35°C), in combination with prolonged UV-illumination, caused cell shortening, probably because of the phototoxicity of the compound and the formation of rigor crossbridges. We conclude that KB-R7943 may be a useful tool to study cellular Mg2+ homeostasis if care is taken to minimize its phototoxicity.
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