Relationship between extra- and intracellular calcium in distal segments of the renal tubule. Role of the Ca2+ receptor RaKCaR.
The effect of extracellular calcium ([Ca2+]e) on cytosolic calcium ([Ca2+]i) was investigated in thick ascending limbs and collecting ducts from the rat kidney, using the fluorescent dye fura-2. In cortical collecting ducts, basolateral but not apical changes in [Ca2+]e were associated with parallel changes in [Ca2+]i. Basal [Ca2+]i was hardly modified by nifedipine and verapamil but was decreased by 60% by basolateral La3+. Increasing peritubular [Ca2+]e triggered Ca2+ release from intracellular stores. This effect was not reproduced by agonists of the renal Ca2+-receptor RaKCaR, e.g., Ba2+, Mg2+, Gd3+, and neomycin, but was reproduced by Ni2+. Ni2+-induced mobilization of intracellular Ca2+ was larger in the inner medullary collecting duct, a segment which poorly responds to increasing [Ca2+]e. In the cortical thick ascending limb, removing basolateral Ca2+ hardly altered [Ca2+]i but increasing [Ca2+]e or adding Ba2+, Mg2+, Gd3+ and neomycin released intracellular calcium. These data demonstrate that (1) basolateral influx of calcium occurs in cortical collecting ducts, under basal conditions; (2) this influx occurs through nonvoltage gated channels, permeable to Ba2+, insensitive to verapamil and nifedipine, and blocked by La3+; (3) increasing [Ca2+]e stimulates the influx and triggers intracellular calcium release, independently of the phospholipase C-coupled receptor RaKCaR; (4) RaKCaR is functionally expressed in thick ascending limbs; (5) another membrane receptor, sensitive to Ni2+ but not to Ca2+ is present in the collecting duct.
Champigneulle
A
A
CNRS URA 1859, DBCM, SBCe, CEA Saclay, F-91991, Gif-sur-Yvette cedex, France.
Siga
E
E
Vassent
G
G
Imbert-Teboul
M
M
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002413:Cations, Divalent / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000378:metabolism*; D008138:Loop of Henle / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009355:Neomycin / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000819:agonists / Q000502:physiology*; D015290:Second Messenger Systems; D019831:Sodium-Calcium Exchanger; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002352:Carrier Proteins; D002413:Cations, Divalent; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D019831:Sodium-Calcium Exchanger; C473605:extracellular calcium cation-sensing receptor, rat; D014700:Verapamil; D009355:Neomycin; D009543:Nifedipine; D002118:Calcium