title: The leak mode of type II Na(+)-P(i) cotransporters.
abstract: Na(+)-coupled phosphate cotransporters of the SLC34 gene family catalyze the movement of inorganic phosphate (P(i)) across epithelia by using the free energy of the downhill electrochemical Na(+) gradient across the luminal membrane. Electrogenic (NaPi-IIa/b) and electroneutral (NaPi-IIc) isoforms prefer divalent P(i) and show strict Na(+):P(i) stoichiometries of 3:1 and 2:1, respectively. For electrogenic cotransport, one charge is translocated per transport cycle. When NaPi-IIa or NaPi-IIb are expressed in Xenopus oocytes, application of the P(i) transport inhibitor phosphonoformic acid (PFA) blocks a leak current that is not detectable in the electroneutral isoform. In this review, we present the experimental evidence that this transport-independent leak originates from a Na(+)-dependent uniport carrier mode intrinsic to NaPi-IIa/b isoforms. Our findings, based on the characteristics of the PFA-inhibitable leak measured from wild-type and mutant constructs, can be incorporated into an alternating access class model in which the leak and cotransport modes are mutually exclusive and share common kinetic partial reactions.
authors.affiliation: Institute of Physiology and Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Olga
authors.initials: O
authors.lastname: Andrini
authors.forename: Chiara
authors.initials: C
authors.lastname: Ghezzi
authors.forename: Heini
authors.initials: H
authors.lastname: Murer
authors.forename: Ian C
authors.initials: IC
authors.lastname: Forster
mesh_terms: D000818:Animals; D006801:Humans; D017136:Ion Transport; D010539:Permeability; D020033:Protein Isoforms; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000378:metabolism*; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb