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Novel Na<sub>V</sub>1.6-Mitochondrial Complexes in Retinal Astrocyte Pockets Sequester GABA.

Overview

Authors: Joseph Matthew Holden1, David John Calkins1
ORCID iDs: Joseph Matthew Holden, David John Calkins
  1. Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Institutions: Vanderbilt University Medical Center (United States)
Journal: Glia, volume 74, issue 11, article e70238
Dates: received 17 April 2026; accepted 19 September 2026; published online 23 September 2026; in print November 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1002/glia.70238 · PMID 42779159 · PMCID PMC13601821 · OpenAlex W7214153371
Open access: hybrid, a free copy (OpenAlex)
Status: data only (how the code is found and verified)
Categories: mouse (organism), cellular / molecular (subfield)
Methods: Statistics, fMRI & imaging
MeSH: Astrocytes*, gamma-Aminobutyric Acid*, Mitochondria*, NAV1.6 Voltage-Gated Sodium Channel*, Retina*, Animals, Cells, Cultured, Mice, Mice, Inbred C57BL, Retinal Ganglion Cells (* major topic)
Topic: Ion channel regulation and function (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: NIH HHS (DK20593, CA68485, DK58404, DK59637); NIDDK NIH HHS (P30 DK020593, P30 DK058404, U24 DK059637); NEI NIH HHS (5R01EY024997, EY08126, P30 EY008126, R01 EY024997); NCI NIH HHS (P30 CA068485)
Citations: not cited yet (Europe PMC); 26 references in the paper

Abstract

Voltage‐gated sodium channels are best known for their capacity to generate and propagate electrical currents in neurons and muscle. Their expression in glial cells may also be of great importance given these cells' involvement in various disease processes. Here we identify a previously unrecognized voltage‐gated sodium channel NaV1.6‐enriched microdomain in mouse retinal astrocytes. Using super‐resolution confocal microscopy, electrophysiology, and transcriptomic analyses, we show that NaV1.6 forms high‐density clusters within intracellular compartments devoid of the calcium‐binding protein, S100β, typically understood to distribute throughout the entire astrocyte. These NaV1.6 pockets are polarized, clustering only on the bilayer facing retinal ganglion cell neurons, and are packed with unusually large, anaplerotic, and relatively depolarized mitochondria that closely appose NaV1.6 puncta. These metabolic compartments also accumulate high levels of GABA. Together, our findings reveal a specialized NaV1.6‐mitochondrial complex in retinal astrocytes that expands the functional repertoire of voltage‐gated sodium channels beyond direct neuronal electrical excitability.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data and to no code of its authors: see the Data section.

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Data

Datasets cited

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 1 November 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 2 authors, 10 MeSH terms, 4 funders, 26 references.

Cite

This paper

Holden, J. M., & Calkins, D. J. (2026). Novel Na<sub>V</sub>1.6-Mitochondrial Complexes in Retinal Astrocyte Pockets Sequester GABA. Glia, 74(11), e70238. https://doi.org/10.1002/glia.70238

BibTeX

@article{holden2026novel,
author = {Holden, Joseph Matthew and Calkins, David John},
title = {{Novel Na\<sub\>V\</sub\>1.6-Mitochondrial Complexes in Retinal Astrocyte Pockets Sequester GABA}},
journal = {Glia},
year = {2026},
month = nov,
volume = {74},
number = {11},
pages = {e70238},
publisher = {Wiley},
issn = {0894-1491},
doi = {10.1002/glia.70238},
url = {https://doi.org/10.1002/glia.70238},
pmid = {42779159},
pmcid = {PMC13601821}
}

RIS

TY - JOUR
AU - Holden, Joseph Matthew
AU - Calkins, David John
TI - Novel Na<sub>V</sub>1.6-Mitochondrial Complexes in Retinal Astrocyte Pockets Sequester GABA
T2 - Glia
J2 - Glia
PY - 2026
DA - 2026/11/01
VL - 74
IS - 11
SP - e70238
SN - 0894-1491
PB - Wiley
DO - 10.1002/glia.70238
UR - https://doi.org/10.1002/glia.70238
LA - en
ER -

CSL-JSON

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