Hydrogen sulfide regulates hippocampal neuron excitability via S-sulfhydration of Kv2.1

Hydrogen sulfide (H 2 S) is gaining interest as a mammalian signalling molecule with wide ranging effects. S-sulfhydration is one mechanism that is emerging as a key post translational modification through which H 2 S acts. Ion channels and neuronal receptors are key target proteins for S-sulfhydrat...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2021-04, Vol.11 (1), p.8194-11, Article 8194
Main Authors: Dallas, Mark L., Al-Owais, Moza M., Hettiarachchi, Nishani T., Vandiver, Matthew Scott, Jarosz-Griffiths, Heledd H., Scragg, Jason L., Boyle, John P., Steele, Derek, Peers, Chris
Format: Article
Language:English
Subjects:
631/378/2586
631/443/376
631/80/458
Action potential
Action Potentials
Animals
Cells, Cultured
Central nervous system
Down-Regulation
Excitability
Experiments
Glucose
HEK293 Cells
Hippocampus
Hippocampus - cytology
Hippocampus - drug effects
Hippocampus - metabolism
Humanities and Social Sciences
Humans
Hydrogen
Hydrogen sulfide
Hydrogen Sulfide - pharmacology
Ion channels
Medical research
Morpholines - pharmacology
multidisciplinary
Nervous system
Neurons
Neurons - cytology
Neurons - drug effects
Neurons - metabolism
Organothiophosphorus Compounds - pharmacology
Phosphorylation
Physiology
Potassium channels (voltage-gated)
Primary Cell Culture
Proteins
Rats
Regulation
Science
Science (multidisciplinary)
Shab Potassium Channels - genetics
Shab Potassium Channels - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Hydrogen sulfide (H 2 S) is gaining interest as a mammalian signalling molecule with wide ranging effects. S-sulfhydration is one mechanism that is emerging as a key post translational modification through which H 2 S acts. Ion channels and neuronal receptors are key target proteins for S-sulfhydration and this can influence a range of neuronal functions. Voltage-gated K + channels, including Kv2.1, are fundamental components of neuronal excitability. Here, we show that both recombinant and native rat Kv2.1 channels are inhibited by the H 2 S donors, NaHS and GYY4137. Biochemical investigations revealed that NaHS treatment leads to S-sulfhydration of the full length wild type Kv2.1 protein which was absent (as was functional regulation by H 2 S) in the C73A mutant form of the channel. Functional experiments utilising primary rat hippocampal neurons indicated that NaHS augments action potential firing and thereby increases neuronal excitability. These studies highlight an important role for H 2 S in shaping cellular excitability through S-sulfhydration of Kv2.1 at C73 within the central nervous system.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-87646-5