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Connexin and pannexin hemichannels in brain glial cells: properties, pharmacology, and roles.

Giaume C, Leybaert L, Naus CC, Sáez JC - Front Pharmacol (2013)

Bottom Line: They form multimeric membrane channels with pharmacology somewhat overlapping with that of Cx hemichannels.Such duality has led to several controversies in the literature concerning the identification of the molecular channel constituents (Cxs versus Panxs) in glia.In the present review, we update and discuss the knowledge of Cx hemichannels and Panx channels in glia, their properties and pharmacology, as well as the understanding of their contribution to neuroglial interactions in brain health and disease.

View Article: PubMed Central - PubMed

Affiliation: Collège de France, Center for Interdisciplinary Research in Biology/Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241/Institut National de la Santé et de la Recherche Médicale U1050 Paris, France ; University Pierre et Marie Curie Paris, France ; MEMOLIFE Laboratory of Excellence and Paris Science Lettre Research University Paris, France.

ABSTRACT
Functional interaction between neurons and glia is an exciting field that has expanded tremendously during the past decade. Such partnership has multiple impacts on neuronal activity and survival. Indeed, numerous findings indicate that glial cells interact tightly with neurons in physiological as well as pathological situations. One typical feature of glial cells is their high expression level of gap junction protein subunits, named connexins (Cxs), thus the membrane channels they form may contribute to neuroglial interaction that impacts neuronal activity and survival. While the participation of gap junction channels in neuroglial interactions has been regularly reviewed in the past, the other channel function of Cxs, i.e., hemichannels located at the cell surface, has only recently received attention. Gap junction channels provide the basis for a unique direct cell-to-cell communication, whereas Cx hemichannels allow the exchange of ions and signaling molecules between the cytoplasm and the extracellular medium, thus supporting autocrine and paracrine communication through a process referred to as "gliotransmission," as well as uptake and release of metabolites. More recently, another family of proteins, termed pannexins (Panxs), has been identified. These proteins share similar membrane topology but no sequence homology with Cxs. They form multimeric membrane channels with pharmacology somewhat overlapping with that of Cx hemichannels. Such duality has led to several controversies in the literature concerning the identification of the molecular channel constituents (Cxs versus Panxs) in glia. In the present review, we update and discuss the knowledge of Cx hemichannels and Panx channels in glia, their properties and pharmacology, as well as the understanding of their contribution to neuroglial interactions in brain health and disease.

No MeSH data available.


Schematic showing that connexins can from both hemichannels and gap junction channels. In contrast, pannexins normally form channels equivalent to hemichannels. See text for details (provided by Stephen Bond, Ph.D., UBC).
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Figure 1: Schematic showing that connexins can from both hemichannels and gap junction channels. In contrast, pannexins normally form channels equivalent to hemichannels. See text for details (provided by Stephen Bond, Ph.D., UBC).

Mentions: Gap junctions provide a unique direct conduit between cells, influencing crucial cellular processes through activities including electrical conductance and metabolic cooperation, mediated by the passage of ions, amino acids, glucose, glutathione, ATP, and small signaling molecules (reviewed in Sohl and Willecke, 2004), as well as microRNAs (Katakowski et al., 2010). When one considers Cx expression in the brain (Theis et al., 2005), it is evident that they are most abundant in glia, namely the astrocytes, oligodendrocytes, and microglia (Rouach et al., 2002). With the genomic characterization of Cx (Willecke et al., 2002) and Panx (Baranova et al., 2004) gene families, it has been determined that there are at least 10 Cxs and 2 Panxs expressed in the brain (see below). There is also a temporal (i.e., developmental) and spatial (i.e., cell type and brain region) pattern regarding this expression and localization. Furthermore, these channel proteins can have different roles in different cell types, either as the canonical gap junction intercellular channel or as a hemichannel (Goodenough and Paul, 2003; Figure 1). Cx hemichannels and Panx1 channels mediate the release of ATP that activates P2 receptors, promoting rises in intracellular Ca2+ concentrations; gap junction channels mediate the intercellular transfer of second messenger propagated calcium signal (Suadicani et al., 2004; Anselmi et al., 2008; Leybaert and Sanderson, 2012). Under pathological conditions, Panx1 channels have been proposed to mediate activation of the inflammasome both in neurons and astrocytes (Iglesias et al., 2009; Silverman et al., 2009), whereas Cx43 hemichannels are involved in acceleration of astroglia and neuronal cell death triggered by hypoxia-reoxygenation in high glucose (Orellana et al., 2010) and β-amyloid peptide, respectively (Orellana et al., 2011b,c). A further level of complexity can be envisioned in the context of Cxs, where the heteromeric assembly of different Cx proteins into a single channel can result in distinct differences in biophysical properties (Bevans et al., 1998; Harris, 2007). This feature is also true for Panxs since Panx1 can form both homomeric and heteromeric channels with Panx2 (Bruzzone et al., 2005). Thus for specific cellular functions, the complement of Cxs and Panxs expressed is important in the physiological or pathological context being considered. While other “non-channel” functions are emerging for Cxs (Vinken et al., 2012) and Panxs (MacVicar and Thompson, 2010), this review will be limited to channel-related functions and properties.


Connexin and pannexin hemichannels in brain glial cells: properties, pharmacology, and roles.

Giaume C, Leybaert L, Naus CC, Sáez JC - Front Pharmacol (2013)

Schematic showing that connexins can from both hemichannels and gap junction channels. In contrast, pannexins normally form channels equivalent to hemichannels. See text for details (provided by Stephen Bond, Ph.D., UBC).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3713369&req=5

Figure 1: Schematic showing that connexins can from both hemichannels and gap junction channels. In contrast, pannexins normally form channels equivalent to hemichannels. See text for details (provided by Stephen Bond, Ph.D., UBC).
Mentions: Gap junctions provide a unique direct conduit between cells, influencing crucial cellular processes through activities including electrical conductance and metabolic cooperation, mediated by the passage of ions, amino acids, glucose, glutathione, ATP, and small signaling molecules (reviewed in Sohl and Willecke, 2004), as well as microRNAs (Katakowski et al., 2010). When one considers Cx expression in the brain (Theis et al., 2005), it is evident that they are most abundant in glia, namely the astrocytes, oligodendrocytes, and microglia (Rouach et al., 2002). With the genomic characterization of Cx (Willecke et al., 2002) and Panx (Baranova et al., 2004) gene families, it has been determined that there are at least 10 Cxs and 2 Panxs expressed in the brain (see below). There is also a temporal (i.e., developmental) and spatial (i.e., cell type and brain region) pattern regarding this expression and localization. Furthermore, these channel proteins can have different roles in different cell types, either as the canonical gap junction intercellular channel or as a hemichannel (Goodenough and Paul, 2003; Figure 1). Cx hemichannels and Panx1 channels mediate the release of ATP that activates P2 receptors, promoting rises in intracellular Ca2+ concentrations; gap junction channels mediate the intercellular transfer of second messenger propagated calcium signal (Suadicani et al., 2004; Anselmi et al., 2008; Leybaert and Sanderson, 2012). Under pathological conditions, Panx1 channels have been proposed to mediate activation of the inflammasome both in neurons and astrocytes (Iglesias et al., 2009; Silverman et al., 2009), whereas Cx43 hemichannels are involved in acceleration of astroglia and neuronal cell death triggered by hypoxia-reoxygenation in high glucose (Orellana et al., 2010) and β-amyloid peptide, respectively (Orellana et al., 2011b,c). A further level of complexity can be envisioned in the context of Cxs, where the heteromeric assembly of different Cx proteins into a single channel can result in distinct differences in biophysical properties (Bevans et al., 1998; Harris, 2007). This feature is also true for Panxs since Panx1 can form both homomeric and heteromeric channels with Panx2 (Bruzzone et al., 2005). Thus for specific cellular functions, the complement of Cxs and Panxs expressed is important in the physiological or pathological context being considered. While other “non-channel” functions are emerging for Cxs (Vinken et al., 2012) and Panxs (MacVicar and Thompson, 2010), this review will be limited to channel-related functions and properties.

Bottom Line: They form multimeric membrane channels with pharmacology somewhat overlapping with that of Cx hemichannels.Such duality has led to several controversies in the literature concerning the identification of the molecular channel constituents (Cxs versus Panxs) in glia.In the present review, we update and discuss the knowledge of Cx hemichannels and Panx channels in glia, their properties and pharmacology, as well as the understanding of their contribution to neuroglial interactions in brain health and disease.

View Article: PubMed Central - PubMed

Affiliation: Collège de France, Center for Interdisciplinary Research in Biology/Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241/Institut National de la Santé et de la Recherche Médicale U1050 Paris, France ; University Pierre et Marie Curie Paris, France ; MEMOLIFE Laboratory of Excellence and Paris Science Lettre Research University Paris, France.

ABSTRACT
Functional interaction between neurons and glia is an exciting field that has expanded tremendously during the past decade. Such partnership has multiple impacts on neuronal activity and survival. Indeed, numerous findings indicate that glial cells interact tightly with neurons in physiological as well as pathological situations. One typical feature of glial cells is their high expression level of gap junction protein subunits, named connexins (Cxs), thus the membrane channels they form may contribute to neuroglial interaction that impacts neuronal activity and survival. While the participation of gap junction channels in neuroglial interactions has been regularly reviewed in the past, the other channel function of Cxs, i.e., hemichannels located at the cell surface, has only recently received attention. Gap junction channels provide the basis for a unique direct cell-to-cell communication, whereas Cx hemichannels allow the exchange of ions and signaling molecules between the cytoplasm and the extracellular medium, thus supporting autocrine and paracrine communication through a process referred to as "gliotransmission," as well as uptake and release of metabolites. More recently, another family of proteins, termed pannexins (Panxs), has been identified. These proteins share similar membrane topology but no sequence homology with Cxs. They form multimeric membrane channels with pharmacology somewhat overlapping with that of Cx hemichannels. Such duality has led to several controversies in the literature concerning the identification of the molecular channel constituents (Cxs versus Panxs) in glia. In the present review, we update and discuss the knowledge of Cx hemichannels and Panx channels in glia, their properties and pharmacology, as well as the understanding of their contribution to neuroglial interactions in brain health and disease.

No MeSH data available.