# Glial ion channels in glia/neurons interactions.

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2021 · $335,781

## Abstract

Isolated microenvironments like the synapse exist throughout the nervous system where the concentration of
ions is regulated by accessory cells, including glia, quite independently from the surrounding tissues. The ionic
composition of these microenvironments is key for neuronal function. Despite the fact that glial regulation of ion
concentration in microenvironments is a main mode for regulating neuronal activity, our understanding of this
type of regulation by glia is limited, especially for ions like Cl- and HCO3-. Furthermore, models are lacking
where a comprehensive analysis can be performed on the glial ion channels and transporters involved in
regulating ion concentrations, and how these proteins impact neuronal output, from molecule to animal
behavior. In our over 10 years of effort aimed at advancing understanding of glia-neurons interaction and its
impact on animal behavior using the model C. elegans, we have recently taken the unbiased approach of
sequencing the mRNA of Amphid sheath glia. In this application, we propose to establish the mechanism by
which one of the identified enriched genes, the glial Cl-/HCO3- permeable channel CLH-1, regulates neuronal
output and animal behavior. We previously published that CLH-1 mediates pH regulation in the worm nervous
system. Our preliminary results now show that CLH-1 is needed for normal nose-touch behavior. We
hypothesize that glial CLH-1 regulates the activity of touch neurons via a direct effect of the permeating ions Cl-
and HCO3- on neuronal DEG-1 channels. Thus, the specific aims of this application are: 1) In neurons, to
establish the mechanism of neuronal dysfunction when clh-1 is knocked-out, 2) In glia, to determine whether it
is the loss of permeation of Cl-, HCO3-, or both that produces the phenotype of clh-1 knock-out worms.
Furthermore, in aim 3 we will exploit our proven approach to identify additional glial ion channels and
transporter genes that are critical for the glial control of neuronal function and animal behavior: 3) To identify
novel glial ion channels and transporters involved in glia-neurons interaction. The importance of regulating ion
concentrations in neuronal microenvironments is underscored by the fact that several neurological diseases
such as deafness, epilepsy, Alzheimer's, and even demyelinating diseases like multiple sclerosis are
characterized by loss of ionic homeostasis. We propose here to use methodologies we have developed and
proven to be effective to test mechanisms by which dysregulation of Cl- and HCO3- homeostasis in C. elegans
leads to severe neuronal pathology. In addition, we will test the involvement of newly identified genes encoding
glial channels and transporters in glia-neurons interaction.

## Key facts

- **NIH application ID:** 10105211
- **Project number:** 5R01NS105616-04
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Laura Bianchi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $335,781
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10105211

## Citation

> US National Institutes of Health, RePORTER application 10105211, Glial ion channels in glia/neurons interactions. (5R01NS105616-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10105211. Licensed CC0.

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