pannexons

Pannexons are large-pore membrane channels formed by the pannexin family of proteins, notably Panx1, Panx2, and Panx3. These channels assemble as hexamers in the plasma membrane and function as non-junctional channels that release ATP and other small signaling molecules into the extracellular space, contributing to purinergic signaling and intercellular communication.

Structure and localization: Pannexins have four transmembrane domains, two extracellular loops that can be glycosylated, and cytoplasmic N- and C- termini. Glycosylation of Panx1’s extracellular loop limits gap-junction formation, so pannexins usually operate as plasma membrane channels rather than intercellular conduits. Panx2 is enriched in the central nervous system and often localizes to intracellular membranes, whereas Panx3 is expressed in skin and other tissues and can form plasma membrane channels in some contexts.

Activation and regulation: Channels can be opened by changes in membrane potential, mechanical stress, and intracellular calcium; Panx1 can be activated by caspase-3/7 cleavage during apoptosis, which creates a constitutively active channel that promotes ATP release.

Functions and roles: The principal function is the release of ATP and other metabolites to regulate purinergic receptors, influence synaptic activity, and modulate inflammatory responses. In immune and CNS cells, Panx channels participate in inflammasome signaling, cytokine release, and microglial activation; in development and injury, they contribute to cell death signaling and tissue homeostasis.

Inhibition and research context: Pharmacological inhibitors such as carbenoxolone and probenecid are commonly used but lack complete specificity, complicating interpretation of results. Genetic deletion studies in mice support a role for pannexins in inflammation and neuronal injury, but findings vary by tissue and context. Research into pannexons continues to clarify their diverse roles and assess their viability as drug targets.