Connexin Expression (Gap Junctions and Hemichannels) in Astrocytes

Scemes, Eliana; Spray, David C.

doi:10.1007/978-0-387-79492-1_5

Cited by 7 publications

(7 citation statements)

References 260 publications

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“…Since then, a growing body of evidence suggests that through this form of signaling, astrocytes can interact with other glial cells, neurons and endothelial cells in the CNS, thereby modulating synaptic transmission and mediating neurovascular coupling (Nedergaard et al , 2003; Haydon and Carmignoto, 2006; Scemes and Giaume, 2006; Scemes and Spray, 2008). …”

Section: Discussionmentioning

confidence: 99%

“…Intercellular calcium waves (ICWs) provide a mechanism for long-range signaling between astrocytes (see Scemes and Giaume, 2006; Scemes and Spray, 2008 for reviews). Transmission of ICWs can involve both gap junction-mediated direct cytosol-to-cytosol diffusion of second messengers such as IP 3 and Ca 2+ , and release of molecules such as ATP that diffuse through extracellular space, interacting with receptors on neighboring cells to mobilize calcium from the intracellular and extracellular compartments (Scemes and Giaume, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…SGCs in both dorsal root and trigeminal ganglia are coupled by gap junctions (Hanani et al , 2002; Cherkas et al , 2004; Huang et al , 2005) and express purinergic receptors (Weick et al , 2003; Zhang et al , 2007; Ceruti et al , 2008). The presence of these receptors is noteworthy as they have been shown to be involved in the extracellular mediation of ICW spread in astrocytes (Scemes and Giaume, 2006; Scemes and Spray, 2008). Also, SGCs possess mechanisms for release of cytokines (Takeda et al , 2007; Zhang et al , 2007) and possibly other chemical messengers.…”

Section: Introductionmentioning

confidence: 99%

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Bidirectional calcium signaling between satellite glial cells and neurons in cultured mouse trigeminal ganglia

et al. 2009

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Astrocytes communicate with neurons, endothelial and other glial cells through transmission of intercellular calcium signals. Satellite glial cells (SGCs) in sensory ganglia share several properties with astrocytes, but whether this type of communication occurs between SGCs and sensory neurons has not been explored. In the present work we used cultured neurons and SGCs from mouse trigeminal ganglia to address this question. Focal electrical or mechanical stimulation of single neurons in trigeminal ganglion cultures increased intracellular calcium concentration in these cells and triggered calcium elevations in adjacent glial cells. Similar to neurons, SGCs responded to mechanical stimulation with increase in cytosolic calcium that spread to the adjacent neuron and neighboring glial cells. Calcium signaling from SGCs to neurons and among SGCs was diminished in the presence of the broad-spectrum P2 receptor antagonist suramin (50 µM) or in the presence of the gap junction blocker carbenoxolone (100 µM), whereas signaling from neurons to SGCs was reduced by suramin, but not by carbenoxolone. Following induction of submandibular inflammation by Complete Freund's Adjuvant injection, the amplitude of signaling among SGCs and from SGCs to neuron was increased, whereas the amplitude from neuron to SGCs was reduced. These results indicate for the first time the presence of bidirectional calcium signaling between neurons and SGCs in sensory ganglia cultures, which is mediated by the activation of purinergic P2 receptors, and to some extent by gap junctions. Furthermore, the results indicate that not only sensory neurons, but also SGCs release ATP. This form of intercellular calcium signaling likely plays key roles in the modulation of neuronal activity within sensory ganglia in normal and pathological states.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bidirectional calcium signaling between satellite glial cells and neurons in cultured mouse trigeminal ganglia

et al. 2009

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“…For instance, following postnatal development, Cx43 together with Cx30 are mainly found in astrocytes, whereas Cx29, Cx32, and Cx47 form the oligodendrocyte group of gap junction proteins, and Cx36, Cx45, and Cx30.2 are expressed in neurons (for review, see Ref. 13). …”

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confidence: 99%

The Carboxyl-terminal Domain of Connexin43 Is a Negative Modulator of Neuronal Differentiation

Santiago

Alcamí

Striedinger

et al. 2010

Journal of Biological Chemistry

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Connexin43 (Cx43) is widely expressed in embryonic brain, and its expression becomes restricted mainly to astrocytes as the central nervous system matures. Recent studies have indicated that Cx43 plays important, nonchannel, roles during central nervous system development by affecting neuronal cell migration. Here, we evaluated the effects of Cx43 on neuronal differentiation. For that we used an in vitro model of neural cell development (neurospheres) to evaluate, through immunocytochemistry, electrophysiology, and molecular biology, the degree of neuronal maturation from neurospheres derived from wild-type (WT) and Cx43-null mice. Our results indicate that Cx43 is a negative modulator of neuronal differentiation. The percent neurospheres containing differentiated neurons and the number of cells displaying inward currents were significantly higher in Cx43-null than in WT littermate neurospheres. Knockdown of Cx43 with small interfering RNA increased the number of WT neurospheres generating differentiated neurons. Blockade of gap junctional communication with carbenoxolone did not induce neuronal differentiation in WT neurospheres. Transfection of Cx43-null neurospheres with Cx43 mutants revealed that Cx43 carboxyl terminus prevents neuronal maturation. In agreement with these in vitro data, in situ analysis of embryonic day 16 brains revealed increased ␤-III-tubulin expression in germinal zones of Cx43-null compared with that of WT littermates. These results indicate that Cx43, and specifically its carboxyl terminus, is crucial for signaling mechanisms preventing premature neuronal differentiation during embryonic brain development.Multiple distinct mechanisms contribute to neocortical development. Diffusible and nondiffusible molecules have been implicated in neural cell proliferation, migration, and differentiation during brain development (1-4). Connexins (Cx), 2 the proteins forming gap junctions, are prominent in neural progenitor cells and play important roles in neural cell proliferation, migration, and differentiation (5-9). Among the central nervous system gap junction proteins, Cx43 and Cx26 are the two most abundantly expressed in neural stem cells, although transcripts for other connexins (Cx29, Cx30, Cx30.2, Cx32, Cx36, and Cx47) are also present in embryonic states (10 -12). The expression pattern of connexin proteins dramatically changes as the central nervous system matures, becoming restricted with respect to cell type. For instance, following postnatal development, Cx43 together with Cx30 are mainly found in astrocytes, whereas Cx29, Cx32, and Cx47 form the oligodendrocyte group of gap junction proteins, and Cx36, Cx45, and Cx30.2 are expressed in neurons (for review, see Ref. 13).The dramatic decrease in Cx43 expression during central nervous system development, specifically during neuroblast maturation, has raised the possibility that concurrent loss of gap junctional communication may play an important role during neuronal differentiation. Indeed, initial studies (14, 15) indicating an inver...

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“…Studies on a wide range of non-excitable cell types and under a wide range of conditions has made it clear that two distinct processes contribute to long range cell signaling: direct intercellular diffusion of second messenger molecules through gap junction channels (most likely IP 3 , although Ca 2+ and other molecules may also contribute) and a nonjunctional pathway in which ATP and other molecules are released from a stimulated cell to act on membrane receptors of adjacent cells [1]. With respect to ATP, its release can elevate Ca 2+ in adjacent cells through activation of both metabotropic and ionotropic purinergic P2 receptors.…”

Section: Introductionmentioning

confidence: 99%

Pannexin1-Mediated ATP Release Provides Signal Transmission Between Neuro2A Cells

Iglesias

Spray

2012

Neurochem Res

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Pannexin1 (Panx1), a protein related to the gap junction proteins of invertebrates, forms nonjunctional channels that open upon depolarization and in response to mechanical stretch and purinergic receptor stimulation. Importantly, ATP can be released through Panx1 channels, providing a possible role for these channels in non-vesicular signal transmission. In this study we expressed exogenous human and mouse Panx1 in the gap junction deficient Neuro2A neuroblastoma cell line and explored the contribution of Panx1 channels to cell–cell communication as sites of ATP release. Electrophysiological (patch clamp) recordings from Panx1 transfected Neuro2A cells revealed membrane conductance that increased beyond 0 mV when applying voltage ramps from −60 to +100 mV; threshold was correlated with extracellular K+, so that at 10 mM K+, channels began to open at −30 mV. Evaluation of cell–cell communication using dual whole cell recordings from cell pairs revealed that activation of Panx1 current in one cell of the pair induced an inward current in the second cell after a latency of 10–20 s. This paracrine response was amplified by an ATPase inhibitor (ARL67156, 100 µM) and was blocked by the ATP-degrading enzyme apyrase (6.7 U/ml), by the P2 receptor antagonist suramin (50 µM) and by the Panx1 channel blocker carbenoxolone. These results provide additional evidence that ATP release through Panx1 channels can mediate nonsynaptic bidirectional intercellular communication. Furthermore, current potentiation by elevated K+ provides a mechanism for enhancement of ATP release under pathological conditions.

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Connexin Expression (Gap Junctions and Hemichannels) in Astrocytes

Cited by 7 publications

References 260 publications

Bidirectional calcium signaling between satellite glial cells and neurons in cultured mouse trigeminal ganglia

Bidirectional calcium signaling between satellite glial cells and neurons in cultured mouse trigeminal ganglia

The Carboxyl-terminal Domain of Connexin43 Is a Negative Modulator of Neuronal Differentiation

Pannexin1-Mediated ATP Release Provides Signal Transmission Between Neuro2A Cells

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