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Tubular flow activates magnesium transport in the distal convoluted tubule

Magnesium (Mg2+) is an important cofactor of many enzymes crucial for life; therefore, maintaining a Mg2+ balance in the body is essential. In the kidney, the distal convoluted tubule (DCT) determines the final urinary Mg2+ excretion. The nephron is subjected to variable urinary flow, but little is known about the influence of flow on Mg2+ transport. Primary cilia, which are mechanosensory organelles that sense changes in flow, are expressed on tubular epithelial cells. This study aimed to elucidate whether urinary flow facilitates DCT Mg2+ transport. To this end, mouse DCT15 cells, with and without primary cilia, were exposed to physiologic fluid flow generating 0.3, 0.6, and 1.2 dyn/cm2 fluid shear stress (FSS). FSS stimulated Mg2+ uptake significantly. Net Mg2+ uptake (i.e., the difference between static and FSS) followed a single component saturable first‐order transport function and was independent of FSS magnitude and primary cilia. FSS did not affect the expression of magnesiotropic genes, including Cnnm2, Kcna1, Proegf, Trpm6, and Trpm7. Transient receptor potential cation channel subfamily melastatin (TRPM) member 7 (Trmp7) inhibition by 2‐aminoethyl diphenyl borinate or knockout of TRPM6 did not alter net Mg2+ uptake, suggesting that TRPM6/TRPM7 homo/heterodimeric channels are not involved in FSS‐activated Mg2+ transport. In summary, FSS generated by physiologic fluid flow is a new factor activating Mg2+ transport in DCT independent of primary cilia.—Verschuren, E. H. J., Hoenderop, J. G. J., Peters, D. J. M., Arjona, F. J., Bindels, R. J. M. Tubular flow activates magnesium transport in the distal convoluted tubule. FASEB J. 33, 5034–5044 (2019). www.fasebj.org