Selective serotonin reuptake inhibitors (SSRIs) suppress Na⁺- dependent Mg²⁺ efflux in rat ventricular myocytes

Na⁺/Mg²⁺ exchange transport, the Na⁺ gradient-driven Mg²⁺ extrusion system, plays a key role in cellular Mg²⁺ homeostasis. To date, the molecular entity and selective inhibitors of Na⁺/Mg²⁺ exchanger have not been fully explored. Intracellular free Mg²⁺ concentration ([Mg²⁺]_i) was measured in ventricular myocytes acutely isolated from rat hearts. After soaking the cells in high-Mg²⁺ low-Na⁺ solution to increase [Mg²⁺]_i, the addition of extracellular Na⁺ caused a decrease in [Mg²⁺]_i. We analyzed the rate of decrease in [Mg²⁺]_i as Na⁺/Mg²⁺ exchange transport activity. The suppression of the rate of decrease in [Mg²⁺]_i caused by sertraline, a selective serotonin reuptake inhibitor (SSRI), was concentration dependent (IC₅₀ 8.9 μM) and reversible. Other SSRIs, namely paroxetine and fluvoxamine, were less effective than sertraline. In conclusion, sertraline inhibited Na⁺/Mg²⁺ exchange transport more effectively than any previously reported inhibitors of Na⁺/Mg²⁺ exchanger. Sertraline could be used as a tool to characterize the functions of Na⁺/Mg²⁺ exchanger.