Abstract
Gap junctions (GJs) are hemichannels on cell membrane. Once they are intercellulary connected to the neighboring cells, they build a functional syncytium which allows rapid transfer of ions and molecules between cells. This characteristic makes GJs a potential modulator in proliferation, migration, and development of the cells. So far, several types of GJs are recognized on different brain cells as well as in glioma. Astrocytes, as one of the major cells that maintain neuronal homeostasis, express different types of GJs that let them communicate with neurons, oligodendrocytes, and endothelial cells of the blood brain barrier; however, the main GJ in astrocytes is connexin 43. There are different cerebral diseases in which astrocyte GJs might play a role. Several drugs have been reported to modulate gap junctional communication in the brain which can consequently have beneficial or detrimental effects on the course of treatment in certain diseases. However, the exact cellular mechanism behind those pharmaceutical efficacies on GJs is not well-understood. Accordingly, how specific drugs would affect GJs and what some consequent specific brain diseases would be are the interests of the authors of this chapter. We would focus on pharmaceutical effects on GJs on astrocytes in specific diseases where GJs could possibly play a role including: (1) migraine and a novel therapy for migraine with aura, (2) neuroautoimmune diseases and immunomodulatory drugs in the treatment of demyelinating diseases of the central nervous system such as multiple sclerosis, (3) glioma and antineoplastic and anti-inflammatory agents that are used in treating brain tumors, and (4) epilepsy and anticonvulsants that are widely used for seizures therapy. All of the above-mentioned therapeutic categories can possibly affect GJs expression of astrocytes and the role is discussed in the upcoming chapter.
Highlights
Gap junctions (GJs) are composed of 12 subunits of connexin (Cx) in a way that each six connexins compose one connexon
The mechanism of its effect is not fully understood, the available data suggest a strong role for GJs that are connecting neurons and satellite ganglion cells in trigeminal nerve
Whether gap junctional communication (GJC) inhibition is the main pharmacological mechanism of Tonabersat in human is the subject of further studies
Summary
Gap junctions (GJs) are composed of 12 subunits of connexin (Cx) in a way that each six connexins compose one connexon. GJs possess some general features, they exhibit specific characteristics depending on the subtypes, cell types and tissues. Besides the role as a channel, GJs may exhibit hemichannel activity, which is independent of their channel permeability characteristics. Hemichannel activity of GJs refers to actions that do not require the formation of a channel between opposing connexons of the neighboring cells. The inflammatory stimulus oppositely modulates the hemichannel and channel activity of Cx43 on both astrocytes and C6 glioma cell lines (De Vuyst et al, 2007; Retamal et al, 2007). Hemichannel features of GJs have major roles in cytoskeletal organization and rapid normalization of toxic levels of Ca2+ as well as cell proliferation, migration, adhesion, and differentiation during development. Authors will explore the effects of therapeutic agents on astrocytes’ GJs in migraine, demyelinating disease of the central nervous system (CNS), glioma and epilepsy
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