Open AccessKB-R7943 inhibits Na+-dependent Mg2+ efflux in rat ventricular myocytes
Author(s) -
Michiko Tashiro,
Hirokazu Inoue,
Masato Konishi
Publication year - 2010
Publication title -
journal of physiological sciences
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.968
H-Index - 49
eISSN - 1880-6562
pISSN - 1880-6546
DOI - 10.1007/s12576-010-0113-z
Subject(s) - chemistry , efflux , phototoxicity , biophysics , homeostasis , inhibitory postsynaptic potential , pharmacology , imipramine , sodium calcium exchanger , myocyte , biochemistry , microbiology and biotechnology , endocrinology , in vitro , biology , medicine , intracellular , alternative medicine , pathology
Na(+)-dependent Mg(2+) efflux activity was studied with the fluorescent Mg(2+) 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(+)/Ca(2+) exchange, most potently inhibited the Na(+)/Mg(2+) exchange with half inhibitory concentrations (IC(50)) of 21 μM: (25°C) and 16 μM: (35°C). These IC(50) values were a factor of three to four lower than those of imipramine, a widely used inhibitor of Na(+)/Mg(2+) exchange. Apart from the inhibitory effect on Na(+)/Mg(2+) 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 Mg(2+) homeostasis if care is taken to minimize its phototoxicity.