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Sci Rep. 2017 Apr 19;7:46619. doi: 10.1038/srep46619.

Current carried by the Slc26 family member prestin does not flow through the transporter pathway.

Author information

1
Dept. of Neurology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510 USA.
2
Dept. of Surgery, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510 USA.
3
Yale Center for Analytical Sciences, Yale School of Public Health, 300 George St., Ste Suite 555, New Haven, CT 06511, USA.
4
Dept. of Cellular and Molecular Physiology, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA.
5
Dept. of, Neuroscience, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA.

Abstract

Prestin in the lateral membrane of outer hair cells, is responsible for electromotility (EM) and a corresponding nonlinear capacitance (NLC). Prestin's voltage sensitivity is influenced by intracellular chloride. A regulator of intracellular chloride is a stretch-sensitive, non-selective conductance within the lateral membrane, GmetL. We determine that prestin itself possesses a stretch-sensitive, non-selective conductance that is largest in the presence of thiocyanate ions. This conductance is independent of the anion transporter mechanism. Prestin has been modeled, based on structural data from related anion transporters (SLC26Dg and UraA), to have a 7 + 7 inverted repeat structure with anion transport initiated by chloride binding at the intracellular cleft. Mutation of residues that bind intracellular chloride, and salicylate treatment which prevents chloride binding, have no effect on thiocyanate conductance. In contrast, other mutations reduce the conductance while preserving NLC. When superimposed on prestin's structure, the location of these mutations indicates that the ion permeation pathway lies between the core and gate ring of helices, distinct from the transporter pathway. The uncoupled current is reminiscent of an omega current in voltage-gated ion channels. We suggest that prestin itself is the main regulator of intracellular chloride concentration via a route distinct from its transporter pathway.

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