Connexin and pannexin hemichannels of neurons and astrocytes

Thompson, Roger; MacVicar, Brian A.

doi:10.4161/chan.2.2.6003

Cited by 95 publications

(76 citation statements)

References 70 publications

(105 reference statements)

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“…Indeed, pannexin-mediated efflux of ATP has been described for erythrocytes and taste cells (Locovei et al, 2006;Huang et al, 2007). Interestingly, in hippocampal pyramidal cells, pannexin-1 is expressed at postsynaptic densities (Ray et al, 2005;Zoidl et al, 2007) in which it may serve as a conduit for the transfer of molecules such as ATP and possibly glutamate (Thompson and Macvicar, 2008). Consistent with a role of pannexins in mediating signaling that modulates astrocyte calcium responses, application of the pannexin inhibitor probenecid (Silverman et al, 2008) reduced both the percentage of responding astrocytes and the frequency of their calcium events.…”

Section: Discussionmentioning

confidence: 99%

“…7 A, B), we investigated other pathways that may lead to increased extracellular ATP and glutamate signaling in response to neuronal activity. Among these pathways, release of ATP and possibly glutamate through neuronal pannexin hemichannels has been postulated (Thompson and Macvicar, 2008). Indeed, ATP release through pannexin-1 has been demonstrated in non-neuronal cells (Bao et al, 2004;Locovei et al, 2006;Huang et al, 2007).…”

Section: Mapping Astrocyte Responses To Neuronal Stimulationmentioning

confidence: 99%

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Astrocytes Display Complex and Localized Calcium Responses to Single-Neuron Stimulation in the Hippocampus

Bernardinelli

Salmon²,

Jones³

et al. 2011

Journal of Neuroscience

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Astrocytes show a complex structural and physiological interplay with neurons and respond to neuronal activation in vitro and in vivo with intracellular calcium elevations. These calcium changes enable astrocytes to modulate synaptic transmission and plasticity through various mechanisms. However, the response pattern of astrocytes to single neuronal depolarization events still remains unresolved. This information is critical for fully understanding the coordinated network of neuron-glial signaling in the brain. To address this, we developed a system to map astrocyte calcium responses along apical dendrites of CA1 pyramidal neurons in hippocampal slices using single-neuron stimulation with channelrhodopsin-2. This technique allowed selective neuronal depolarization without invasive manipulations known to alter calcium levels in astrocytes. Light-evoked neuronal depolarization was elicited and calcium events in surrounding astrocytes were monitored using the calcium-sensitive dye Calcium Orange. Stimulation of single neurons caused calcium responses in populations of astrocytes along the apical axis of CA1 cell dendrites. Calcium responses included single events that were synchronized with neuronal stimulation and poststimulus changes in calcium event frequency, both of which were modulated by glutamatergic and purinergic signaling. Individual astrocytes near CA1 cells showed low ability to respond to repeated neuronal depolarization events. However, the response of the surrounding astrocyte population was remarkably accurate. Interestingly, the reliability of responses was graded with respect to astrocyte location along the CA1 cell dendrite, with astrocytes residing in the primary dendrite subregion being most responsive. This study provides a new perspective on the dynamic response property of astrocyte ensembles to neuronal activity.

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Section: Discussionmentioning

confidence: 99%

Section: Mapping Astrocyte Responses To Neuronal Stimulationmentioning

confidence: 99%

Astrocytes Display Complex and Localized Calcium Responses to Single-Neuron Stimulation in the Hippocampus

Bernardinelli

Salmon²,

Jones³

et al. 2011

Journal of Neuroscience

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“…Connexin (Cx) subunits are the building blocks of vertebrate gap junction channels [110][111][112][113]. More than 20 human connexin isoforms have been identified, with predicted size of individual species ranging from 23 to 62 kDa and, accordingly, referred as to Cxn, where n denotes the molecular weight (e.g., Cx30, Cx43).…”

Section: Connexinsmentioning

confidence: 99%

Vesicular and conductive mechanisms of nucleotide release

Lazarowski

2012

Purinergic Signalling

254

225

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Extracellular nucleotides and nucleosides promote a vast range of physiological responses, via activation of cell surface purinergic receptors. Virtually all tissues and cell types exhibit regulated release of ATP, which, in many cases, is accompanied by the release of uridine nucleotides. Given the relevance of extracellular nucleotide/nucleoside-evoked responses, understanding how ATP and other nucleotides are released from cells is an important physiological question. By facilitating the entry of cytosolic nucleotides into the secretory pathway, recently identified vesicular nucleotide and nucleotide-sugar transporters contribute to the exocytotic release of ATP and UDP-sugars not only from endocrine/exocrine tissues, but also from cell types in which secretory granules have not been biochemically characterized. In addition, plasma membrane connexin hemichannels, pannexin channels, and less-well molecularly defined ATP conducting anion channels have been shown to contribute to the release of ATP (and UTP) under a variety of conditions.

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“…Because first observations of hemichannel activity were in an oocyte expression system (Paul et al 1991) and dissociated retinal horizontal cells (DeVries and Schwartz 1992), the possible functions of hemichannels composed of connexins and pannexins has enjoyed vigorous investigation Bennett et al 2003;Locovei et al 2006;Evans et al 2006;Srinivas et al 2007;Schenk et al 2008;Thompson and MacVicar 2008;Anselmi et al 2008;Goodenough and Paul 2003). Hemichannels have been implicated in various forms of paracrine signaling, for example in providing a pathway for extracellular release of ATP (Cotrina et al 1998;Kang et al 2008), glutamate (Ye et al 2003), NAD þ (Bruzzone et al 2000), and prostaglandins (Jiang and Cherian 2003).…”

mentioning

confidence: 99%