Top panel: Nephron segmentation, including the TAL and the DCT subsegments DCT1 and DCT2. Note that the transition from DCT1 to DCT2 is gradual. Middle panel: Transport pathways in these segments include Na⁺/K⁺-ATPase (~), the furosemide-sensitive Na⁺K⁺2Cl cotransporter (NKCC2), the Cl^– channel (CLCNKB), the epithelial Na⁺ channel (ENaC), and the thiazide-sensitive NaCl cotransporter (NCC). Mg²⁺ transport along the TAL is primarily paracellular. Along the DCT, however, it is mediated by TRPM6. Two K⁺ channels are present in the apical membrane: ROMK and, as shown by Glaudemans et al. in this issue of the JCI (5), Kv1.1 (see text for further details). K⁺ and Cl^– can exit DCT cells via a coupled K⁺/Cl^– cotransporter (KCC4) or a discrete K⁺ channel. Lower panel: Membrane voltages along each segment, in millivolts (mV). The basolateral voltage is similar in each cell type. V_TE, transepithelial voltage. As postulated by Glaudemans et al. (5), a defective Kv1.1 (indicated by red X) should depolarize the apical membrane (red bars) along the DCT, leading to hyperpolarization of the transepithelial voltage.