Functional evidence for a Ca2+/polyvalent cation sensor in the mouse thick ascending limb
Paulais, M.; Baudouin-Legros, M.; Teulon, J.
American Journal of Physiology 271(5 Pt 2): F1052-F1060
1996
ISSN/ISBN: 0002-9513 PMID: 8946000 Document Number: 456000
The effects of extracellular polyvalent cations on the cytosolic free Ca-2+ concentration ((Ca-2+)-i) of isolated segments of the mouse nephron were investigated using fura 2 microfluorometry. Extracellular Ca-2+ concentration ((Ca-2+)-o), gadolinium (Gd-3+), and neomycin (Neo) increased the (Ca-2+)-i in cortical thick ascending limb (CTAL) tubules with effective doses (ED-50) of apprx 3.5 mM for Ca-2+, 20 mu-M for Gd-3+, and 40 mu-M for Neo. This effect was reproduced by Ba-2+ but not by Mg-2+. High (Ca-2+)-o inhibited the responses to Gd-3+, Neo, and Ba-2+. The Gd-3+- and Neo-evoked (Ca-2+)-i transients persisted in the absence of external Ca-2+ and were abolished by the depletion of internal Ca-2+ stores with thapsigargin (TG). The responses to rises in (Ca-2+)-o were similarly inhibited by TG and slightly reduced by 20 mu-M La-3+ but not by 10 mu-M nifedipine. Mn-2+ also mobilized a TG-sensitive internal Ca-2+ store and stimulated its own entry. External Ca-2+, Gd-3+, and Neo induced small but significant increases in (Ca-2+)-i in distal convoluted tubule, cortical collecting duct, and outer medullary collecting duct segments, transiently increased (Ca-2+)-i in some medullary TAL (MTAL) tubules, but had no effect on descending thin limb. We conclude that a Ca-2+-mobilizing Ca-2+/polyvalent cation sensor resembling that of the parathyroid gland cells is predominantly located in the mouse CTAL but also in the MTAL and, to a lesser extent, in more distal segments.