ASIC1a-Dependent Potentiation of Acid-Sensing Ion Channel Currents by Cyanide

ASIC1a-Dependent Potentiation of Acid-Sensing Ion Channel Currents by Cyanide

Cyanide (CN) is a potent, fast-acting toxicant that impacts endogenous biomolecules in the nervous system, including acid-sensing ion channels (ASICs), which play a vital role in various neurological and psychological conditions. Here, we demonstrate that CN rapidly potentiates ASIC currents in cult...

Full description

Saved in:
Bibliographic Details
Main Authors: Qian Jiang, Felix Yang, Amber Sun, Yuyang Chu, Joseph Cascone, Dylan Glaser, Xiang-Ping Chu
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Biomolecules
Subjects:
acid-sensing ion channels
cyanide
zinc
point mutation
patch-clamp recording
cultured cortical neuron
Online Access:https://www.mdpi.com/2218-273X/15/4/479
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cyanide (CN) is a potent, fast-acting toxicant that impacts endogenous biomolecules in the nervous system, including acid-sensing ion channels (ASICs), which play a vital role in various neurological and psychological conditions. Here, we demonstrate that CN rapidly potentiates ASIC currents in cultured mouse cortical neurons in a dose-dependent manner while causing a leftward shift in the pH dose–response curve. Notably, this potentiation was unaffected by a 30-min CN treatment or the presence of ATP in the recording pipette. Further investigations into the role of zinc revealed that TPEN, a high-affinity zinc chelator, did not enhance ASIC currents following CN pretreatment, nor did CN influence the potentiation of ASIC currents induced by TPEN. Low-affinity zinc blocked the potentiation of ASIC currents by CN. CN potentiated ASIC currents in cortical neurons from ASIC2 but not from ASIC1a knockout mice. In experiments with CHO cells expressing homomeric ASIC1a and heteromeric ASIC1a/2, CN potentiated ASIC1a currents but had no effect on homomeric ASIC1b, ASIC2a, or ASIC3 channels. Mutating lysine 133 (K133) to arginine (R) in the extracellular domain of ASIC1a abolished CN’s effect, suggesting that CN potentiates ASIC1a currents primarily via high-affinity zinc binding, with K133 being critical for this modulation.
ISSN:2218-273X

Similar Items