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

## TL;DR

This study shows that sertraline, an SSRI antidepressant, strongly inhibits a key magnesium transport system in heart cells.

## Contribution

Sertraline is identified as the most potent known inhibitor of Na+/Mg2+ exchanger in ventricular myocytes.

## Key findings

- Sertraline concentration-dependently suppresses Na+/Mg2+ exchange transport with an IC50 of 8.9 μM.
- Sertraline inhibition of Na+/Mg2+ exchange is reversible and more effective than previously reported inhibitors.
- Other SSRIs like paroxetine and fluvoxamine are less effective than sertraline in suppressing this transport.

## Abstract

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.

•Na+/Mg2+ exchange transport plays a key role in cellular Mg2+ homeostasis.•We found that Na+/Mg2+ exchanger is inhibited by SSRIs, including sertraline.•Sertraline is the most potent inhibitor of Na+/Mg2+ exchanger reported to date.•Sertraline is a useful tool to characterize the functions of Na+/Mg2+ exchanger.

Na+/Mg2+ exchange transport plays a key role in cellular Mg2+ homeostasis.

We found that Na+/Mg2+ exchanger is inhibited by SSRIs, including sertraline.

Sertraline is the most potent inhibitor of Na+/Mg2+ exchanger reported to date.

Sertraline is a useful tool to characterize the functions of Na+/Mg2+ exchanger.