Panx1

Pannexin-1 (Panx1) is a membrane channel-forming protein in mammals. It forms large-pore hemichannels that release ATP and other metabolites to the extracellular space, enabling paracrine and autocrine signaling. Panx1 is broadly expressed, with notable presence in neurons, glia, immune cells, and endothelial tissues.

Structure and regulation: Panx1 is a glycoprotein with four transmembrane segments, two extracellular loops, and intracellular N- and C-termini. It assembles as a hexamer to form a functional channel. Activation can be triggered by membrane depolarization, elevated intracellular calcium, mechanical stress, and proteolytic cleavage during apoptosis. Channel opening and ATP release can be linked to signaling through the P2X7 receptor and inflammatory pathways.

Physiological roles: Panx1-mediated ATP release participates in neurotransmission, vasodilation, immune cell activation, and tissue repair. It contributes to inflammasome signaling and can influence pain perception, stroke outcomes, and other inflammatory processes. In the CNS, Panx1 regulates synaptic activity and astrocyte–neuronal communication.

Pharmacology and research: Panx1 activity can be inhibited by several compounds, including probenecid, mefloquine, and carbenoxolone; however, these inhibitors are not entirely specific. Genetic deletion or silencing of Panx1 in animals reduces ATP release and dampens inflammatory responses in certain models, underlining its potential as a therapeutic target. Ongoing studies examine its role in disease and the development of more selective blockers.

Related topics: Panx1 is a member of the pannexin family, which forms channels in vertebrate membranes. Distinct from connexins, pannexins typically function as single-hemichannel units rather than forming gap junctions, although some contexts exhibit different configurations.

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