Pannexin‐1 in the CNS: Emerging concepts in health and disease

Abstract

Pannexin‐1 (Panx1) is a large pore membrane channel with unique conduction properties ranging from non‐selective ion permeability to the extracellular release of signalling molecules. The release of ATP by Panx1 has been particularly well‐characterized with implications in purine signalling across a variety of biological contexts. Panx1 activity is also important in inflammasome formation and the secretion of pro‐inflammatory molecules such as interleukin‐1β. Within the central nervous system (CNS), Panx1 is expressed on both neurons and glia, and is thought to mediate crosstalk between these cells. A growing body of literature now supports the pathological activity of Panx1 in contributing to disease processes including seizure, stroke, migraine headache and chronic pain. Emerging evidence also reveals a physiological function of Panx1 in regulating neural stem cell survival, neuronal maturation and synaptic plasticity, with possible relevance to normal cognitive functioning. The aim of this review is to summarize the current evidence regarding the roles of Panx1 in the CNS, with emphasis on how putative signalling properties and activation mechanisms of this channel contribute to various physiological and pathophysiological processes. image

Superoxide and Non-ionotropic Signaling in Neuronal Excitotoxicity

“…A second and apparently independent role of metabotropic signaling in excitotoxicity involves pannexin channel opening. When activated, pannexin ion channels become permeable to Na + , Ca 2+ , and other ions and molecules (Yeung et al, 2020). Thompson and colleagues have shown that sustained NMDAr activation can induce pannexin-1 channel activation in the absence of ion flux through the NMDAr ion channel, with the resulting Ca 2+ and Na + influx essentially amplify the elevations caused by ion flux through the NMDAr itself.…”

Excitotoxicity: Still Hammering the Ischemic Brain in 2020

“…3. Pannexin ion channels constitute 3 new members of the gap junction superfamily, first cloned from mammalian tissue 20 years ago (Barbe et al, 2006;Yeung et al, 2020). Panx1 is widely expressed on the plasma membrane of central neurons, glia, and endothelial cells.…”

Astroglial Connexins in Neurodegenerative Diseases

“…In addition, the pannexin (Panx) protein family could also perform Cx-hemichannel-like activity (Yeung et al, 2020). Panx usually does not form GJCs (Sosinsky et al, 2011;Sahu et al, 2014) and Panx channels have similar membrane topology and pharmacological properties to Cx hemichannels.…”

“…Panx usually does not form GJCs (Sosinsky et al, 2011;Sahu et al, 2014) and Panx channels have similar membrane topology and pharmacological properties to Cx hemichannels. However, Panx and Cx exhibit no significant sequence homology (Yeung et al, 2020). Panx1 and Panx2 expression have been found in neurons, however, their expression in astrocytes is still controversial, which may depend on the pathological condition (Vogt et al, 2005;Yeung et al, 2020).…”

“…However, Panx and Cx exhibit no significant sequence homology (Yeung et al, 2020). Panx1 and Panx2 expression have been found in neurons, however, their expression in astrocytes is still controversial, which may depend on the pathological condition (Vogt et al, 2005;Yeung et al, 2020). This review will focus on the current understanding of astrocytic Cx in neurodegenerative diseases, including AD, PD, HD, and ALS.…”