Neuroscience Forefront ReviewHemichannels: New pathways for gliotransmitter release

- Glial cell hemichannels can release relevant quantities of gliotransmitters.
- Hemichannel opening could be associated with cell death.
- Cx26 hemichannel-dependent release of ATP mediates chemoreception.
- Cx43 hemichannels participate in brain glucosensing.

Growing evidence suggests that glial cells express virtually all known types of neurotransmitter receptors, enabling them to sense neuronal activity and microenvironment changes by responding locally via the Ca2+-dependent release of bioactive molecules, known as “gliotransmitters”. Several mechanisms of gliotransmitter release have been documented. One of these mechanisms involves the opening of plasma membrane channels, known as hemichannels. These channels are composed of six protein subunits consisting of connexins or pannexins, two highly conserved protein families encoded by 21 or 3 genes, respectively, in humans. Most data indicate that under physiological conditions, glial cell hemichannels have low activity, but this activity is sufficient to ensure the release of relevant quantities of gliotransmitters to the extracellular milieu, including ATP, glutamate, adenosine and glutathione. Nevertheless, it has been suggested that dysregulations of hemichannel properties could be critical in the beginning and during the maintenance of homeostatic imbalances observed in several brain diseases. In this study, we review the current knowledge on the hemichannel-dependent release of gliotransmitters in the physiology and pathophysiology of the CNS.