Pannexin-1 opening in neuronal edema causes cell death but also leads to protection via increased microglia contacts.

ABSTRACT: Neuronal swelling during cytotoxic edema is triggered by Na⁺ and Cl^- entry and is Ca²⁺ independent. However, the causes of neuronal death during swelling are unknown. Here, we investigate the role of large-conductance Pannexin-1 (Panx1) channels in neuronal death during cytotoxic edema. Panx1 channel inhibitors reduce and delay neuronal death in swelling triggered by voltage-gated Na⁺ entry with veratridine. Neuronal swelling causes downstream production of reactive oxygen species (ROS) that opens Panx1 channels. We confirm that ROS activates Panx1 currents with whole-cell electrophysiology and find scavenging ROS is neuroprotective. Panx1 opening and subsequent ATP release attract microglial processes to contact swelling neurons. Depleting micro

SUBMITTER: Weilinger NL 

PROVIDER: S-EPMC10824275 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature