Work

ASIC1a as an integrating node in ischemic neurotoxicity: crosstalk with NMDAR and TRPM signaling

Year: 2026

Type: review

Abstract: Ischemic stroke triggers acidosis, glutamate excitotoxicity and oxidative stress, which converge to disturb ionic homeostasis through several cation channels, including acid-sensing ion channel 1a (ASIC1a), N-methyl-D-aspartate receptors (NMDARs) and transient receptor potential melastatin (TRPM) channels. Emerging evidence suggests that ASIC1a functions as a context-dependent integrating node: protons directly gate ASIC1a, glutamate and bilirubin-associated signaling can modulate ASIC1a-dependent injury pathways. ASIC1a directly couples with NMDAR-dependent signaling and indirectly engages TRPM-associated pathways. Here, we discuss the mechanistic basis, therapeutic potential and unresolved questions regarding ASIC1a-associated signaling in ischemic brain injury.

Source: Pflügers Archiv - European Journal of Physiology

DOI: 10.1007/s00424-026-03225-5

Authors: Ke Lai, Lu-Yang Wang

Institutions: Shanghai Jiao Tong University, Shanghai Sixth People's Hospital, University of Toronto, Sickkids Research Institute

Language: English

Topic: Ion Channels and Receptors

Subfield: Sensory Systems

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,390