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Connexins in the Brain: Psychopharmaceutical Implications

Author(s): Hussam Alsarraf, Kyle A Kelly, Clay Anderson, J Matthew Rhett


Connexins are the channel forming constituents of hemichannels that facilitate cellextracellular communication, and gap junction (GJ) intercellular channels that directly connect the cytoplasm of interacting cells. The role of connexins in the brain is an area of growing interest. The purpose of this review is to highlight the current state of research and where future research might be headed, with particular attention to the role of connexins in psychology and psychiatric pharmaceuticals. The primary connexin isoforms in the brain include connexin45 (Cx45), Cx43, Cx36, and Cx30. These connexins display differential expression in the major neuronal cell types, and have functions including synchronization of neuronal oscillations, metabolite homeostasis, and release of gliotransmitters. Importantly, these processes utilize both GJ intercellular communication, and hemichannel cell-extracellular communication pathways. At the behavioral level, connexins in the brain have been shown to be involved in memory, alcohol indulgence, motor coordination, and anxiety.


There are many compounds that broadly inhibit connexins, and a handful of targeted, isoform-specific, channel function agonists and antagonists. However, these compounds have primarily researched in areas other than the brain. Therefore, connexins potentially provide new pharmaceutical targets for psychiatric disorders.

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