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Updated: Jun 28, 2026

Application of Electrophysiology Measurement to Study the Activity of Electro-Neutral Transporters
Published on: February 3, 2018
The leak mode of type II Na(+)-P(i) cotransporters
Olga Andrini1, Chiara Ghezzi, Heini Murer
1Institute of Physiology and Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
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.
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