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

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. Pannexin‐1 (Panx1) is a channel which is best recognized for releasing ATP across the plasma membrane. It is also known to facilitate large non‐selective ion currents and mediate inflammasome activation. In this review, we highlight our current understanding of Panx1 function in CNS physiology and pathophysiology. We discuss the implications of Panx1 activity in the crosstalk between neurons, glia, peripheral immune cells and the vasculature. New insights in this area of study may enable the development of therapeutics targeting Panx1 in disorders of the CNS.