Selective serotonin reuptake inhibitors (SSRIs) suppress Na- dependent Mg efflux in rat ventricular myocytes.

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