Distinct thick ascending limb cell types mediate divalent and monovalent ion transport

The kidney thick ascending limb (TAL) is typically viewed as comprising a single cell type that expresses a Na-K-2Cl transporter and potassium channel at the apical membrane and a basolateral chloride channel. Together, these generate a lumen-positive transepithelial voltage. This review summarizes recent work revising this view substantially.

Very early work suggested that not all TAL cells express potassium channels at the apical membrane. More recently, it became clear that paracellular transport pathways for monovalent and divalent cations exhibit a mosaic pattern, suggesting further diversity. By combining transcriptomics with more established approaches, it has become clear that there are 3 types of TAL cells. One type resembles the classic model. A second type, in the cortex and parts of the outer medulla, however, does not express apical potassium channels and is ringed by claudins that transport calcium and magnesium. A third type, in the inner stripe of the outer medulla, also lacks apical potassium channels but exhibits sodium-permeable claudins within the tight junctions.

Previously unrecognized distinct cell types along the TAL mediate sodium transport and calcium/magnesium transport separately. Each type expresses regulatory pathways to permit differential regulation thereby preserving homeostasis.