1 research outputs found
pH-Regulated Nonelectrogenic Anion Transport by Phenylthiosemicarbazones
Gated ion transport across biological
membranes is an intrinsic
process regulated by protein channels. Synthetic anion carriers (anionophores)
have potential applications in biological research; however, previously
reported examples are mostly nonspecific, capable of mediating both
electrogenic and electroneutral (nonelectrogenic) transport processes.
Here we show the transmembrane Cl<sup>–</sup> transport studies
of synthetic phenylthiosemicarbazones mimicking the function of acid-sensing
(proton-gated) ion channels. These anionophores have remarkable pH-switchable
transport properties with up to 640-fold increase in transport efficacy
on going from pH 7.2 to 4.0. This “gated” process is
triggered by protonation of the imino nitrogen and concomitant conformational
change of the anion-binding thiourea moiety from anti to syn. By using
a combination of two cationophore-coupled transport assays, with either
monensin or valinomycin, we have elucidated the fundamental transport
mechanism of phenylthiosemicarbazones which is shown to be nonelectrogenic,
inseparable H<sup>+</sup>/Cl<sup>–</sup> cotransport. This
study demonstrates the first examples of pH-switchable nonelectrogenic
anion transporters