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Functional characterization of human SLC41A1, a Mg²⁺ transporter with similarity to prokaryotic MgtE Mg²⁺ transporters

Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

We have begun to identify and characterize genes that are differentially expressed with low magnesium. One of these sequences conformed to the solute carrier SLC41A1. Real-time RT-PCR of RNA isolated from renal distal tubule epithelial [mouse distal convoluted tubule (MDCT)] cells cultured in low-magnesium media relative to normal media and in the kidney cortex of mice maintained on low-magnesium diets compared with those animals consuming normal diets confirmed that the SLC41A1 transcript is responsive to magnesium. Mouse SLC41A1 was cloned from MDCT cells, expressed in Xenopus laevis oocytes, and studied with two-electrode voltage-clamp studies. When expressed in oocytes, SLC41A1 mediates saturable Mg²⁺ uptake with a Michaelis constant of 0.67 mM. Transport of Mg²⁺ by SLC41A1 is rheogenic, voltage dependent, and not coupled to Na⁺or Cl^–. Expressed SLC41A1 transports a range of other divalent cations: Mg²⁺, Sr²⁺, Zn²⁺, Cu²⁺, Fe²⁺, Co²⁺, Ba²⁺, and Cd²⁺. The divalent cations Ca²⁺, Mn²⁺, and Ni²⁺ and the trivalent ion Gd³⁺ did not induce currents nor did they inhibit Mg²⁺ transport. The nonselective cation La³⁺ abolished Mg²⁺ uptake. The SLC41A1 transcript is present in many tissues, notably renal epithelial cells, and is upregulated in some tissues with magnesium deficiency. These studies suggest that SLC41A1 is a regulated Mg²⁺ transporter that might be involved in magnesium homeostasis in epithelial cells.

magnesium; differentially regulated; expression; Xenopus oocytes

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