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1 Institute of Anatomy, University of Zurich, CH-8057 Zurich; 2 Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520; 3 Institut de Pharmacologie et de Toxicologie, Université de Lausanne, CH-1005 Lausanne, Switzerland; and 4 Department of Cell Physiology, University Medical Centre, 6500-HB Nijmegen, The Netherlands
First published August
15, 2001; 10.1152/ajprenal. 00085.2001.
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
thiazide-sensitive Na+-Cl
cotransporter (NCC)
characterized the distal convoluted tubule (DCT). The
amiloride-sensitive epithelial Na+ channel (ENaC)
colocalized with NCC in late DCT (DCT2) and extended to the downstream
connecting tubule (CNT) and collecting duct (CD). In early DCT (DCT1),
the basolateral Ca2+-extruding proteins
[Na+/Ca2+ exchanger (NCX), plasma membrane
Ca2+-ATPase (PCMA)] and the cytoplasmic
Ca2+-binding protein calbindin D28K (CB) were
found at very low levels, whereas the cytoplasmic
Ca2+/Mg2+-binding 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
cytoplasmic at the end of CNT. NCX and PMCA decreased in parallel with
the fading of ECaC1 in the apical membrane. All three of them were
undetectable in 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 transport regulation.
mouse kidney morphology; amiloride-sensitive epithelial sodium channel; thiazide-sensitive sodium-chloride cotransporter; epithelial calcium channel; calcium-binding proteins
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