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Current Medicinal Chemistry
ISSN (Print): 0929-8673
ISSN (Online): 1875-533X
Epub Full Text Article
DOI: 10.2174/0929867321666131228191714      Price:  $95









Role of Connexins and Pannexins in Ischemic Stroke

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Author(s): Juan A. Orellana, Beatriz C. Avendaño and Trinidad D. Montero
Abstract:
Synaptic plasticity requires the careful synchronization and coordination of neurons and glial cells via various mechanisms of intercellular communication. Among them, are those mediated by i) connexin gap junction channels (GJCs), ii) connexin hemichannels and iii) pannexin channels. Whereas GJCs directly communicate the cytoplasm of contacting cells and coordinate electric and metabolic activities, connexin hemichannels and pannexin channels serve as diffusional pathways for ions and small molecules between the intra- and extracellular compartments. A growing body of evidence has revealed that intercellular communication could be critical in the spread of protective and/or deleterious signals during stroke. Here, we review the current findings on the regulation of connexin- and pannexin-based channels in ischemic stroke and how they contribute to cell damage observed in pathology. Depending on the intensity of the ischemia, brain region and connexin subtype expressed, GJCs may provide the proper diffusion of energy metabolites and dissipation of toxic substances, whereas, in other circumstances, they could increase the damage by spreading toxic molecules. Alternatively, connexin hemichannel and pannexin channel opening may favor the release of neurotoxic substances (e.g., glutamate), but in other cases, they may confer neuroprotection against an ischemic episode by the phenomenon of ischemic preconditioning. The development of new drug modulators using in silico devices for connexin and pannexin-based channels will be crucial for future therapies against stroke
Keywords:
Hemichannels, pannexin channels, gap junctions, ischemia, brain, glia, neurons
Affiliation:
Departamento de Neurología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, Chile