KB-R7943 inhibits Na+-dependent Mg2+ efflux in rat ventricular myocytes.
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.
Tashiro
Michiko
M
Department of Physiology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
Inoue
Hana
H
Konishi
Masato
M
D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D006358:Hot Temperature; D007099:Imipramine / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D032342:Muscle Cells / Q000187:drug effects* / Q000378:metabolism; D010647:Phenyl Ethers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors; D013890:Thiourea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000814:Aniline Compounds; D010647:Phenyl Ethers; C430918:SEA 0400; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D013890:Thiourea; D008274:Magnesium; D007099:Imipramine