Pannexin

Pannexins are a family of channel-forming glycoproteins that assemble into hexameric channels in the plasma membrane. They create large-pore channels that connect the intracellular space with the extracellular environment, allowing the passage of ions and small signaling molecules such as ATP. In vertebrates, three pannexins have been identified: Panx1, Panx2, and Panx3, encoded by the PANX1-3 genes. Panx1 is widely expressed across tissues, Panx2 is enriched in the central nervous system, and Panx3 is found in skin, bone, and teeth.

Pannexins are often described as forming hemichannels rather than classical intercellular gap junction channels. While connexins commonly pair across adjacent cells to form gap junctions, pannexins predominantly function as single-membrane channels that release signals from the cytoplasm into the extracellular space. Structurally, Panx1 is characterized by extracellular loops that can be N-glycosylated, a feature that influences trafficking and channel properties; Panx2 and Panx3 display different expression and glycosylation patterns that relate to their tissue distribution.

Activation of pannexin channels can occur via mechanical stress, membrane depolarization, and elevated intracellular calcium. A notable mechanism for Panx1 is caspase-3–mediated cleavage during apoptosis, leading to sustained ATP release and involvement in inflammatory signaling. Through ATP and other metabolites, pannexin channels participate in purinergic signaling and can influence neuronal excitability, immune responses, and vascular and sensory processes.

In research, pannexin function is studied with pharmacological inhibitors such as probenecid and various peptides; these tools help explore their roles in inflammation, stroke, pain, and other pathophysiological conditions.