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Review
. 2019 Jan 29:13:3.
doi: 10.3389/fncel.2019.00003. eCollection 2019.

Connexin and Pannexin-Based Channels in Oligodendrocytes: Implications in Brain Health and Disease

Sebastián Vejar  1 , Juan E Oyarzún  2   3 , Mauricio A Retamal  4   5 , Fernando C Ortiz  1 , Juan A Orellana  2   3
Affiliations
Review

Connexin and Pannexin-Based Channels in Oligodendrocytes: Implications in Brain Health and Disease

Sebastián Vejar et al. Front Cell Neurosci. .

Abstract

Oligodendrocytes are the myelin forming cells in the central nervous system (CNS). In addition to this main physiological function, these cells play key roles by providing energy substrates to neurons as well as information required to sustain proper synaptic transmission and plasticity at the CNS. The latter requires a fine coordinated intercellular communication with neurons and other glial cell types, including astrocytes. In mammals, tissue synchronization is mainly mediated by connexins and pannexins, two protein families that underpin the communication among neighboring cells through the formation of different plasma membrane channels. At one end, gap junction channels (GJCs; which are exclusively formed by connexins in vertebrates) connect the cytoplasm of contacting cells allowing electrical and metabolic coupling. At the other end, hemichannels and pannexons (which are formed by connexins and pannexins, respectively) communicate the intra- and extracellular compartments, serving as diffusion pathways of ions and small molecules. Here, we briefly review the current knowledge about the expression and function of hemichannels, pannexons and GJCs in oligodendrocytes, as well as the evidence regarding the possible role of these channels in metabolic and synaptic functions at the CNS. In particular, we focus on oligodendrocyte-astrocyte coupling during axon metabolic support and its implications in brain health and disease.

Keywords: connexons; demyelinating neuropathy; gap junctions; hemichannels; oligodendrocytes; pannexons.

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Figures

Figure 1
Figure 1
Expression of connexins by oligodendrocytes. Representative fluorescence images depicting the double immunostaining of connexin 29 (Cx29; red, left panels), Cx32 (red, middle panels) and Cx47 (red, right panels) with the oligodendrocyte-specific bio-marker myelin basic protein (MBP, green) and DAPI staining (blue) by mature cultured oligodendrocytes after 6 days in vitro. Arrows highlight representative MBP-positive cells. Adapted, with permission, from Niu et al. (2016).
Figure 2
Figure 2
Schematics of possible roles of connexin- and pannexin-based channels in oligodendrocyte function and dysfunction. During high rates of neuronal activity K+ accumulates in the extracellular space, and then is taken up by oligodendrocytes and astrocytes through the inwardly rectifying K+ channel (Kir) 4.1 and/or Na+/K+-pumps (1). K+ that concentrates inside oligodendrocytes and astrocytes diffuses to the panglial syncytium via homocellular and heterocellular gap junction channels (GJCs), a process termed “spatial K+ buffering.” In parallel, neuronal and astroglial signaling (e.g., ATP and glutamate) could activate endothelial P2 and NMDA receptors (NMDARs), respectively, leading to increased free [Ca2+]i and further vasodilation of blood vessels (not depicted). The latter increases cerebral blood flow and further uptake of glucose by astrocytic endfeet (2). Glucose diffuses through astrocytes and oligodendrocytes via homocellular and heterocellular GJCs and then can be metabolized to lactate by astrocytes, and both can be released into the extracellular space. In addition, glucose is taken up by oligodendrocyte precursor cells (OPCs; via an unknown hemichannel) and neurons, which possibly modulate oligodendrocyte differentiation and maturation (3), as well as axonal function (4), respectively. In pathological scenarios, the opening of Panx1 channels may lead to the release of ATP from oligodendrocytes (5), resulting in the activation of P2X7 receptors (P2X7Rs) and further triggering of a self-perpetuating mechanism of cell damage, in which high levels of [Ca2+]i and direct protein-protein interaction could reactivate pannexons. Part of this schematics was done with support of the free online Servier Medical Art repository (https://smart.servier.com/).
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