Connexin Hemichannels: Structure, Function, and Dysfunction

Dear Colleagues,

Connexin (Cx) hemichannels (HCs) are large pore hexameric structures that allow the exchange of ions, metabolites, and a variety of other molecules between cell cytoplasm and extracellular milieu. The opening of HCs promotes the diffusive release of paracrine messengers, including ATP, glutamate, prostaglandins, NAD(+), and glutathione. In several instances, molecules released through open HCs, most importantly ATP, may act as damage-associated molecular patterns (DAMPs), activating inflammatory pathways and promoting cell death. Point mutations that render HCs constitutively more active or abnormally active (referred to also as “leaky” HCs) have been implicated in numerous genetic diseases affecting the facial appearance, dentition (small and carious teeth), eyes (microphthalmia, microcornea), fingers (syndactyly), lens (cataracts), nervous system (myelination defects), heart (atrial fibrillation), inner ear (deafness), and skin (various disorders). In addition, the opening of wild-type (wt) HCs is associated with an impressive list of pathological conditions that affect a major proportion of the world population, including ischemia/stroke, Alzheimer’s disease, epilepsy, liver fibrosis and cirrhosis, nonalcoholic steatohepatitis, inflammation, and others. For these reasons, HC inhibitors are attracting growing interest as drug candidates.

Prof. Dr. Fabio Mammano
Guest Editor

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