# Cellular and Ion Channel Mechanisms Underlying the Sense of Light Touch in Mammals

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $489,359

## Abstract

ABSTRACT:
 The sense of touch is critical for daily tasks including tactile discrimination, social interaction, and
environmental exploration. The overall objective of this project is to identify the cellular and molecular
mechanisms underlying the sense of touch in mammals. Previous studies have shown that Merkel discs, a
main type of tactile end organ, play a central role in the sense of touch. Merkel discs are located in touch
sensitive spots throughout the body especially at human fingertips and whisker hair follicles of non-primate
mammals. A Merkel disc consists of a Merkel cell and an Aβ-afferent ending (Merkel ending) to form a
synapse-like structure. We and others have previous shown that the Piezo2 channel on Merkel cells is the
sensor of touch. We have further shown that tactile stimuli activate Piezo2 channels in Merkel cells to result in
Ca2+-action potentials, which leads to Aβ-afferent impulses and behavioral tactile responses. However, the
mechanism by which tactile-induced excitatory signals on Merkel cells are transmitted to Merkel endings
remains elusive and is the focus of this renewal application. Our central hypothesis is that acid sensing ion
channels (ASICs) are the excitatory postsynaptic receptors and proton is the principal transmitter to mediate
excitatory postsynaptic currents (EPSCs) and synaptic transmission at Merkel discs. We will test this novel
hypothesis with the following specific aims. Aim 1. Characterize the fundamental nature of EPSCs at Merkel
endings of Aβ-afferent fibers. Aim 2. Demonstrate that EPSCs are mediated by ASICs located at Merkel
endings. Aim 3. Elucidate that activation of ASICs by protons is responsible for the generation of EPSCs at
Merkel endings. Aim 4. Identify the isoform of functional ASICs that mediate EPSCs at Merkel endings.
Pressure-patch-clamp recordings will be applied at the heminode of Merkel endings in rodent whisker hair
follicles to record EPSCs that are evoked by mechanical stimulation, and other techniques including synaptic
physiology, pharmacology, immunohistochemistry, and mouse genetics will be used to achieve the above
aims. By completing the above aims, we will have uncovered a new fundamental mechanism mediating
synaptic transmission of tactile signals at Merkel discs. This will significantly advance scientific knowledge
about molecular mechanisms underlying the sense of touch. It may also have important implications in
mechanical sensory dysfunctions (e.g., loss of touch sensation) seen under clinical conditions such as
diabetes and chemotherapy.

## Key facts

- **NIH application ID:** 10865027
- **Project number:** 5R01DE023090-13
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** JIANGUO GU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $489,359
- **Award type:** 5
- **Project period:** 2013-06-12 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10865027

## Citation

> US National Institutes of Health, RePORTER application 10865027, Cellular and Ion Channel Mechanisms Underlying the Sense of Light Touch in Mammals (5R01DE023090-13). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10865027. Licensed CC0.

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