Abstract
Na(+)/Mg(2+) exchange transport, the Na(+) gradient-driven Mg(2+) extrusion system, plays a key role in cellular Mg(2+) homeostasis. To date, the molecular entity and selective inhibitors of Na(+)/Mg(2+) exchanger have not been fully explored. Intracellular free Mg(2+) concentration ([Mg(2+)](i)) was measured in ventricular myocytes acutely isolated from rat hearts. After soaking the cells in high-Mg(2+) low-Na(+) solution to increase [Mg(2+)](i), the addition of extracellular Na(+) caused a decrease in [Mg(2+)](i). We analyzed the rate of decrease in [Mg(2+)](i) as Na(+)/Mg(2+) exchange transport activity. The suppression of the rate of decrease in [Mg(2+)](i) caused by sertraline, a selective serotonin reuptake inhibitor (SSRI), was concentration dependent (IC(50) 8.9 μM) and reversible. Other SSRIs, namely paroxetine and fluvoxamine, were less effective than sertraline. In conclusion, sertraline inhibited Na(+)/Mg(2+) exchange transport more effectively than any previously reported inhibitors of Na(+)/Mg(2+) exchanger. Sertraline could be used as a tool to characterize the functions of Na(+)/Mg(2+) exchanger.