# Electrophysiological basis of sour taste transduction

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $496,958

## Abstract

Project Summary
The broad goal of the proposed experiments is to identify key molecules that allow mammals to detect basic
tastes and generate electrical responses that are conducted to brain regions. Molecular mechanisms of taste
reception have been a subject of intense investigation over the last 30 years, with great strides made in
identifying receptors for bitter, sweet and umami. Much less is known about the nature and function of receptors
for sour, the taste that allows us to detect acids in spoiled foods or citrus fruits. In this proposal, we will begin to
unravel this problem as we test the contribution of the newly discovered otopetrin proton channels in the
transduction of acidic and ionic tastes. These experiments build on the progress made in the last grant
application, where we used a combination of cellular, molecular and functional approaches to identify the pH
sensitive ion channels in Type III taste receptor cells (TRCs) that mediate sour taste. Notably, we described a
novel proton-selective ionic current that is likely to be a key component of sour taste transduction. In the last
funding period, we successfully identified the gene that encodes the proton channel, through functional screening
of genes enriched in Type III TRCs. Among 41 genes tested, we identified one, encoding the transmembrane
protein Otop1 that upon expression induced a proton current in both Xenopus oocytes and HEK-293 cells.
Interestingly, Otop1 was first identified as a gene mutated in mice with vestibular defects (“tilted” or tlt) but its
function in the vestibular system and elsewhere in the body was not understood. Building on these new results,
we propose three specific aims to test the role of the Otop channels in taste signaling. The first aim will examine
the functional distribution of Otop1 across the tongue and palate epithelium, allowing us to answer the question
of whether Otop1 is the sole ion channel mediating proton influx in the gustatory system. In the second aim, we
will measure cellular responses to acids in wildtype and Otop1 KO mice in order to determine the degree to
which Otop1 contributes to sensory responses, ex vivo. In the third aim, we will measure responses from
gustatory nerves and assess behavioral thresholds for acid detection in wildtype and Otop1 KO mice to
determine the extent to which Otop1 mediates responses to sour taste stimuli in vivo. Together our experiments
will allow us to determine if Otop1 functions as a sour taste receptor. Our efforts to identify mechanisms of taste
transduction may allow the development of taste modifiers that can be used to enhance palatability of food,
reducing the need to add sweeteners that contribute to the development of diabetes or salts that contribute to
hypertension. Moreover, the proposed experiments will provide basic information regarding the functional
properties of this new family of proton channels that will help us understand their contributions to diverse
physiological proce...

## Key facts

- **NIH application ID:** 10173740
- **Project number:** 5R01DC013741-08
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Sue C. Kinnamon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $496,958
- **Award type:** 5
- **Project period:** 2014-04-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10173740

## Citation

> US National Institutes of Health, RePORTER application 10173740, Electrophysiological basis of sour taste transduction (5R01DC013741-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10173740. Licensed CC0.

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