Distribution of transcellular calcium and sodium transport pathways along mouse distal nephron

The organization of Na+ and Ca2+ transport pathways along the mouse distal nephron is incompletely known. We revealed by immunohistochemistry a set of Ca2+ and Na+ transport proteins along the mouse distal convolution. The th iazide-sensitive Na+-Cl- cotransporter (NCC) characterized the distal convo luted tubule (DCT). The amiloride-sensitive epithelial Na+ channel (ENaC) c olocalized with NCC in late DCT (DCT2) and extended to the downstream conne cting tubule (CNT) and collecting duct (CD). In early DCT (DCT1), the basol ateral Ca2+-extruding proteins [Na+/Ca2+ exchanger (NCX), plasma membrane C a2+-ATPase (PCMA)] and the cytoplasmic Ca2+-binding protein calbindin D-28K (CB) were found at very low levels, whereas the cytoplasmic Ca2+/Mg2+-bind ing protein parvalbumin was highly abundant. NCX, PMCA, and CB prevailed in DCT2 and CNT, where we located the apical epithelial Ca2+ channel (ECaC1). Its subcellular localization changed from apical in DCT2 to exclusively cy toplasmic at the end of CNT. NCX and PMCA decreased in parallel with the fa ding of ECaC1 in the apical membrane. All three of them were undetectable i n CD. These findings disclose DCT2 and CNT as major sites for transcellular Ca2+ transport in the mouse distal nephron. Cellular colocalization of Ca2 + and Na+ transport pathways suggests their mutual interactions in transpor t regulation.