# Inner ear ion channels in healthy and diseased conditions

> **NIH NIH R01** · UNIVERSITY OF NEVADA RENO · 2020 · $523,352

## Abstract

Abstract:
 Previous studies have demonstrated that the mechanisms underlying the exquisite sensitivity and
frequency selectivity of the cochlea rely partly on the voltage-dependent hair bundle motility and outer hair cell
(OHC) lateral wall electromotility (eM). Several gene products involved in cochlear sound amplification have
been identified, and their mutations have been shown to result in hearing loss in human and mouse models.
For example, mutations of K+ channels (Kv), such as Kv7.4 (critical in controlling OHC membrane excitability)
result in profound progressive hearing loss (PHL: DFNA2). While the global expanse of families with DFNA2
has been identified, the mechanism of the disease is largely unknown. Additionally, the activity of OHCs is
transmitted to the brain via the scarce (~5%) and small diameter, unmyelinated type II auditory neurons (spiral
ganglion neurons (SGNs). These features have made it impractical to isolate and to determine their functional
properties.
 We hypothesize that the properties of Kv7.4 currents in OHCs are achieved by the interaction of Kv7.4 with
KCNE4, the Ca2+ binding protein 2 (CaBP2) and their ability to form clusters. For the first time, we have
developed innovative and painstaking strategies that allow robust assessment of type II auditory neuron
functions.
 We will deploy innovative molecular biology, electrophysiology, imaging techniques, and gene-targeted
mouse models to unravel the fundamental and newly accessible arena of type II SGN/OHC physiology. Aim 1
will identify the molecular determinants for the unique low-voltage-activation properties of Kv7.4 currents in
OHCs. In Aim 2 we will determine the in vivo functions of KCNE4 and CaBP2 in the inner ear. Finally, in Aim 3
we will identify the mechanisms underlying type II neuronal modulation of OHCs.
 The proposed studies will reveal critical missing links of OHC functions and for the first time, determine
features of the scarce type II SGNs that innervate OHCs: therefore, shifting the prevailing monolithic type I
SGN-centric physiology (that is known) to comprehensive understanding of distinct afferent auditory neurons,
information essential for the treatment of sensorineural hearing loss (SNHL).

## Key facts

- **NIH application ID:** 9976492
- **Project number:** 5R01DC016099-04
- **Recipient organization:** UNIVERSITY OF NEVADA RENO
- **Principal Investigator:** EBENEZER N YAMOAH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $523,352
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976492

## Citation

> US National Institutes of Health, RePORTER application 9976492, Inner ear ion channels in healthy and diseased conditions (5R01DC016099-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9976492. Licensed CC0.

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