---
title: "LRRC8A/D VRACs mediate swelling‑activated taurine release in mouse brain"
id: "biorxiv-13-lrrc8a-d-containing-anion-channels-mediate-swelling-activated-taurine-release"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-13-lrrc8a-d-containing-anion-channels-mediate-swelling-activated-taurine-release"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.19.760193v1?rss=1"
published_at: "2026-10-23T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# LRRC8A/D VRACs mediate swelling‑activated taurine release in mouse brain
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-13-lrrc8a-d-containing-anion-channels-mediate-swelling-activated-taurine-release
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.19.760193v1?rss=1)
- **Published At:** 2026-10-23T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Investigators studied swelling‑activated taurine release in mouse brain using RNAi, genetically modified mice, astrocyte cultures, brain microdialysis, and RNA‑seq. - In astrocyte cultures lacking **LRRC8A**, swelling‑activated [3H]**taurine** release was reduced by ~90%, indicating a dominant role for LRRC8A in VRAC function. - Brain‑wide LRRC8A knockout mice (bLRRC8A KO) showed a ≥90% reduction in swelling‑activated taurine release measured by in vivo microdialysis. - Lrrc8d knockdown by RNAi reduced swelling‑activated [3H]taurine efflux by >50%, supporting a specific contribution of **LRRC8D** to osmolyte permeability. - RNA‑seq data indicated enrichment of Lrrc8d expression in the hypothalamus, a region implicated in astrocytic taurine release affecting magnocellular neurons and vasopressin secretion. - To test systemic relevance, investigators challenged mice with intraperitoneal sterile water (7.5% body weight, under anesthesia) and monitored serum osmolality. - Neither brain‑wide LRRC8A knockout nor gene trap–mediated LRRC8D depletion impaired recovery from hypoosmotic challenge, suggesting brain VRAC‑mediated taurine release is not essential for systemic osmoregulation in these models. - The authors declared no competing interests; NIH R21NS140782 provided funding. - The preprint has not been peer reviewed; supplementary material and data/code links are provided by the authors.
## Clinical Analysis & Structured Key Points
LRRC8A/D-containing anion channels mediate swelling-activated taurine release in the mouse brain | bioRxiv Skip to main content New Results LRRC8A/D-containing anion channels mediate swelling-activated taurine release in the mouse brain View ORCID Profile Madison L. Chandler , View ORCID Profile Julia W. Nalwalk , View ORCID Profile Preeti Dohare , View ORCID Profile Ariella D. Sprague , View ORCID Profile Alexandra L. Schober , View ORCID Profile Alexander A. Mongin doi: https://doi.org/10.64898/2026.10.19.760193 Madison L. Chandler 1 Albany Medical College; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Madison L. Chandler Julia W. Nalwalk 1 Albany Medical College; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Julia W. Nalwalk Preeti Dohare 1 Albany Medical College; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Preeti Dohare Ariella D. Sprague 1 Albany Medical College; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ariella D. Sprague Alexandra L. Schober 2 Novartis Institutes for BioMedical Research Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Alexandra L. Schober Alexander A. Mongin 1 Albany Medical College; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Alexander A. Mongin For correspondence: mongina{at}amc.edu Abstract Info/History Metrics Supplementary material Data/Code Preview PDF Abstract Volume-regulated anion channels (VRACs) are swelling-activated Cl⁻ channels formed by heteromers of LRRC8 proteins (LRRC8A-E). VRACs mediate regulatory volume decrease by releasing Cl⁻ and organic osmolytes, including taurine. In the brain, taurine functions as both an osmolyte and an inhibitory neuromodulator, acting as an agonist at glycine and GABAA receptors. Here, we used RNAi and genetically modified mice to (i) determine the contribution of LRRC8 subunits to swelling-activated taurine release, and (ii) test whether brain VRACs contribute to systemic osmoregulation. In astrocyte cultures lacking the essential VRAC subunit LRRC8A, swelling-activated [3H]taurine release was reduced by ~90%. Similarly, in vivo brain microdialysis revealed a ≥90% reduction in swelling-activated taurine release in brain-wide LRRC8A knockout mice (bLRRC8A KO). RNAi experiments further confirmed LRRC8D as a key determinant of VRAC-mediated taurine release, with Lrrc8d knockdown reducing swelling activated [3H]taurine efflux by >50%. RNA-seq revealed enrichment of Lrrc8d in the hypothalamus, where astrocytic taurine release is proposed to inhibit magnocellular neurons and suppress arginine vasopressin secretion during hypoosmotic conditions. We therefore tested whether disrupting brain VRACs impairs recovery from systemic hypoosmotic stress. bLRRC8A KO mice and mice with gene trap-mediated LRRC8D depletion were challenged with an intraperitoneal injection of sterile water (7.5% body weight, under anesthesia), and serum osmolality was monitored over time. Unexpectedly, neither model showed impaired recovery from hypoosmotic challenge. Overall, this study identifies LRRC8A/D-containing VRACs as the primary conduit for swelling-activated taurine release in the brain, yet indicates that this pathway is not essential for maintaining systemic fluid-electrolyte homeostasis. Competing Interest Statement The authors have declared no competing interest. Footnotes https://doi.org/10.17605/OSF.IO/TSZNX https://doi.org/10.6084/m9.figshare.34625250 Funder Information Declared National Institutes of Health , R21NS140782 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Back to top Previous Next Posted October 23, 2026. Download PDF Supplementary Material Data/Code Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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