Preprint
Inhibition of delta-1 glutamate receptor current by extracellular protons
bioRxiv
Cold Spring Harbor Laboratory
07/05/2026
DOI: 10.64898/2026.06.30.735595
PMID: 42427720
Abstract
Decreases in brain pH are associated with numerous neurological and neuropsychiatric conditions yet the molecular mechanisms linking decreased brain pH with these disorders are incomplete. The ionotropic glutamate receptors (iGluRs) mediate the majority of excitatory neurotransmission in the brain and are inhibited by extracellular protons; however, the proton sensitivity of the delta-glutamate receptor subclass of iGluRs is unknown. Using whole-cell patch-clamp recordings of serotonin neurons in mouse brain slices and activating alpha 1-adrenergic receptors to induce delta 1 glutamate receptor (GluD1
) current, we demonstrated that GluD1
current is inhibited by physiological drops in extracellular pH. Unlike other iGluRs, protons inhibited GluD1
current via a voltage-independent decrease in unitary current. Moreover, mice lacking GluD1
showed impaired behavioral responses to inhalation of CO
. Taken together, this study continues to expand on the growing body of evidence positing GluD1
as functional ion channels and suggests that GluD1
facilitate pH sensing
.
Details
- Title: Subtitle
- Inhibition of delta-1 glutamate receptor current by extracellular protons
- Creators
- Andrew G Kain - University of IowaJoe P DeuitchAyank Maiti - University of IowaStephanie C Gantz - University of Iowa
- Resource Type
- Preprint
- Publication Details
- bioRxiv
- DOI
- 10.64898/2026.06.30.735595
- PMID
- 42427720
- NLM abbreviation
- bioRxiv
- ISSN
- 2692-8205
- eISSN
- 2692-8205
- Publisher
- Cold Spring Harbor Laboratory; United States
- Language
- English
- Date posted
- 07/05/2026
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9985180789102771
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