Effect of the antidepressant sertraline on Ca²⁺fluxes in Madin-Darby canine renal tubular cells

The effect of the antidepressant sertraline on cytosolic-free Ca ²⁺ concentrations ([Ca²⁺]i) in Madin Darby canine kidney (MDCK) cells is unclear. This study explored whether sertraline changed basal [Ca²⁺]i levels in suspended MDCK cells by using fura-2 as a Ca ²⁺-sensitive fluorescent dye. Sertraline at concentrations between 1and 100 μM increased [Ca²⁺]i in a concentration-dependent manner. The Ca²⁺ signal was reduced partly by removing extracellular Ca ²⁺ implicating Ca²⁺ entry and release both contributed to the [Ca²⁺]i rise. Sertraline induced Mn2 influx, leading to quench of fura-2 fluorescence, suggesting Ca²⁺influx. This Ca²⁺ influx was inhibited by suppression of phospholiapase A2 but not by store-operated Ca²⁺ channel blockers and protein kinase C/A modulators. In Ca²⁺-free medium, pretreatment with the endoplasmic reticulum Ca²⁺ pump inhibitors nearly abolished sertraline-induced Ca²⁺ release. Conversely, pretreatment with sertraline partly reduced inhibitor-induced [Ca²⁺]i rise, suggesting that sertraline released Ca²⁺ from endoplasmic reticulum. Inhibition of phospholipase C did not much alter sertraline-induced [Ca²⁺]i rise. Collectively, in MDCK cells, sertraline induced [Ca²⁺]i rises by causing phospholipase C-independent Ca²⁺ release from the endoplasmic reticulum and Ca ²⁺ influx via phospholipase A2-sensitive Ca²⁺ channels.