Enhanced sodium-dependent extrusion of magnesium in mutant cells established from a mouse renal tubular cell line.

To study the regulatory mechanisms of intracellular Mg(2+) concentration ([Mg(2+)](i)) in renal tubular cells as well as in other cell types, we established a mutant strain of mouse renal cortical tubular cells that can grow in culture media with very high extracellular Mg(2+) concentrations ([Mg(2+)](o) > 100 mM: 101Mg-tolerant cells). [Mg(2+)](i) was measured with a fluorescent indicator furaptra (mag-fura 2) in wild-type and 101Mg-tolerant cells. The average level of [Mg(2+)](i) in the 101Mg-tolerant cells was kept lower than that in the wild-type cells either at 51 mM or 1 mM [Mg(2+)](o). When [Mg(2+)](o) was lowered from 51 to 1 mM, the decrease in [Mg(2+)](i) was significantly faster in the 101Mg-tolerant cells than in the wild-type cells. These differences between the 101Mg-tolerant cells and the wild-type cells were abolished in the absence of extracellular Na(+) or in the presence of imipramine, a known inhibitor of Na(+)/Mg(2+) exchange. We conclude that Na(+)-dependent Mg(2+) transport activity is enhanced in the 101Mg-tolerant cells. The enhanced Mg(2+) extrusion may prevent [Mg(2+)](i) increase to higher levels and may be responsible for the Mg(2+) tolerance.