The SWELL1 Channel Promotes Ischemic Brain Damage by Mediating Neuronal Swelling and Glutamate Toxicity.

ABSTRACT: Cytotoxic neuronal swelling and glutamate excitotoxicity are two hallmarks of ischemic stroke. However, the underlying molecular mechanisms are not well understood. Here, it is reported that SWELL1, the essential subunit of the volume-regulated anion channel (VRAC), plays a dual role in ischemic injury by promoting neuronal swelling and glutamate excitotoxicity. SWELL1 expression is upregulated in neurons and astrocytes after experimental stroke in mice. The neuronal SWELL1 channel is activated by intracellular hypertonicity, leading to Cl^- influx-dependent cytotoxic neuronal swelling and subsequent cell death. Additionally, the SWELL1 channel in astrocytes mediates pathological glutamate release, indicated by increases in neuronal slow inward current frequency and tonic NMDAR c

SUBMITTER: Chen J 

PROVIDER: S-EPMC11423184 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature