Expression of a renal type I sodium/phosphate transporter (NaPi-1) induces a conductance in Xenopus oocytes permeable for organic and inorganic anions.
Two distinct molecular types (I and II) of renal proximal tubular brush border Na+/Pi cotransporters have been identified by expression cloning on the basis of their capacity to induce Na+-dependent Pi influx in tracer experiments. Whereas the type II transporters (e.g., NaPi-2 and NaPi-3) resemble well known characteristics of brush border Na+/Pi cotransport, little is known about the properties of the type I transporter (NaPi-1). In contrast to type II, type I transporters produced electrogenic transport only at high extracellular Pi concentrations (> or =3 mM). On the other hand, expression of NaPi-1 induced a Cl- conductance in Xenopus laevis oocytes, which was inhibited by Cl- channel blockers [5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) > niflumic acid >> 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid]. Further, the Cl- conductance was inhibited by the organic anions phenol red, benzylpenicillin (penicillin G), and probenecid. These organic anions induced outwardly directed currents in the absence of Cl-. In tracer studies, we observed uptake of benzylpenicillin with a Km of 0.22 mM; benzylpenicillin uptake was inhibited by NPPB and niflumic acid. These findings suggest that the type I Na+/Pi cotransporter functions also as a novel type of anion channel permeable not only for Cl- but also for organic anions. Such an apical anion channel could serve an important role in the transport of Cl- and the excretion of anionic xenobiotics.
Busch
A E
AE
Institute of Physiology I, Eberhard-Karls-Universität Tübingen, Germany.
Schuster
A
A
Waldegger
S
S
Wagner
C A
CA
Zempel
G
G
Broer
S
S
Biber
J
J
Murer
H
H
Lang
F
F
D000818:Animals; D000838:Anions / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism*; D005260:Female; D007687:Kidney Tubules, Proximal / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D008871:Microvilli / Q000502:physiology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010400:Penicillin G / Q000378:metabolism / Q000494:pharmacology; D010637:Phenolsulfonphthalein / Q000378:metabolism / Q000494:pharmacology; D011339:Probenecid / Q000378:metabolism / Q000494:pharmacology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters; D014982:Xenopus laevis
D000838:Anions; D002352:Carrier Proteins; D002712:Chlorides; D011994:Recombinant Proteins; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters; D010637:Phenolsulfonphthalein; D011339:Probenecid; D010400:Penicillin G