# Membrane properties of the OHC system

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $649,745

## Abstract

The cochlea is composed of a variety of cell types including sensory, supporting and neural elements.
Taken together, these cells comprise a functionally intricate and cohesive electrical unit that initiates
the analysis of acoustic information within our environment. We capitalize on the in vitro approach,
including isolated cochlea explants, single cell, and more recently stable cell lines to elucidate cochlear
cell function; the strategy is to characterize basic properties prior to integration into a cohesive
understanding of the organ. Currently, the overarching aim of this project is focused on determining the
biophysical properties of key membrane components of the outer hair cell (OHC), one of the major
players in auditory function, using a balance of electrophysiology, molecular biology, modelling and
high resolution cryo-EM. Though we have made significant progress on many fronts since our last
renewal in 2010, we now focus on three specific research topics that evolve from our most significant
accomplishments. In particular, one of the main areas of our investigations has been and will be the
influence of anions on the OHC molecular motor’s (prestin, SLC26a5) electro-mechanical activity. This
ion is at the root of cochlear amplification (Santos-Sacchi et al., 2006). Indeed, the NIDCD’s 2012-2016
Strategic Plan specifically identifies understanding anion control of hearing as a key goal. The three
aims are 1) to evaluate the chloride-dependent kinetic behavior of OHC nonlinear capacitance and
electromotility, 2) to characterize intracellular chloride movements in the prestin-transfected HEK cell
and OHC with a new prestin-fused YFP chloride sensor we created, and 3) to determine the high
resolution structure of prestin (SLC26a5) and its closest mammalian family member SLC26a6 using
cryo-EM, with the goal of identifying conformational changes due to chloride and voltage. We
hypothesize that understanding these molecular activities will aid in understanding how the OHC
enables us to hear so well and in turn how micro-environmental influences may lead to pathologies of
the OHC that afflict millions.

## Key facts

- **NIH application ID:** 10163155
- **Project number:** 5R01DC016318-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** JOSEPH R SANTOS-SACCHI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $649,745
- **Award type:** 5
- **Project period:** 2017-06-12 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163155

## Citation

> US National Institutes of Health, RePORTER application 10163155, Membrane properties of the OHC system (5R01DC016318-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10163155. Licensed CC0.

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