The participation of plasma membrane hemichannels to purinergic signaling.

The field of hemichannels is closely related to the purinergic signaling and both areas have been growing in parallel. Hemichannels open in response to a wide range of stressful conditions, such as ischemia, pressure or swelling. Hemichannels represent an important mechanism for the cellular release of adenosine 5′-triphosphate (ATP), which is an agonist of the P2Y and P2X family of purinergic receptors. Therefore, hemichannels are key molecules in the regulation of purinergic receptor activation, during physiological and pathophysiological conditions. Furthermore, purinergic receptor activation can also lead to the opening of hemichannels and the subsequent amplification of purinergic signaling via a positive signaling feedback loop, giving rise to the concept of ATP-induced ATP release. Purinergic receptor signaling is involved in regulating many physiological and pathophysiological processes. P2Y receptors activate inositol trisphosphate and transiently increase intracellular calcium. This signaling opens both connexin and pannexin channels, therefore contributing to the expansion of calcium waves across astrocytes and epithelial cells. In addition, several of the P2X receptor subtypes, including the P2X2, P2X4 and P2X7 receptors, activate select cellular permeation pathways to large molecules, including the pannexin-1 channels, which are involved in the initiation of inflammatory responses and cell death. Consequently, the interplay between purinergic receptors and hemichannels could represent a novel target with substantial therapeutic implications in areas such as chronic pain, inflammation or atherosclerosis. This article is part of a Special Issue entitled: The communicating junctions, roles and dysfunctions.