Figure 4.

Schematic of normal Kir4.1/Kir5.1 function in the DCT. Kir4.1/Kir5.1 heteromeric channels are localized in the basolateral membrane, which has numerous deep infoldings. There, the channel ensures that sufficient K⁺ is available to be taken up by the Na⁺/K⁺-ATPase (pump–leak coupling). Moreover, Kir4.1/Kir5.1 channels hyperpolarize the basolateral membrane, generating the driving force for the potential-dependent export of Mg²⁺ and Ca²⁺ and the efflux of Cl⁻ through CLCKB/Barttin Cl⁻ channels. The latter has implications for cytosolic Cl⁻ concentration and is thought to indirectly modulate NCC activity. Ca²⁺ is also extruded basolaterally via Ca²⁺-ATPase (not shown). The molecular nature of the pathway for basolateral Mg²⁺ extrusion is still a matter of debate; likely candidates are shown.