Extracellular ATP Hydrolysis Inhibits Synaptic Transmission by Increasing pH Buffering in the Synaptic Cleft

Vroman, Rozan; Klaassen, Lauw J.; Howlett, Marcus H. C.; Cenedese, Valentina; Klooster, Jan; Sjoerdsma, Trijntje; Kamermans, Maarten

doi:10.1371/journal.pbio.1001864

Cited by 76 publications

(110 citation statements)

References 67 publications

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“…Since sensory inputs to the CNS can be altered in Panx1 −/− mice, as shown recently for the retina (Kranz et al, 2013; Vroman et al, 2014), it was hypothesized that similar changes could be found in other sensory organs. In this study, we characterize the impact of genetic ablation of Panx1 in the olfactory system.…”

Section: Introductionmentioning

confidence: 80%

Investigation of olfactory function in a Panx1 knock out mouse model

Kurtenbach

Whyte-Fagundes

Gelis

et al. 2014

Front. Cell. Neurosci.

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Pannexin 1 (Panx1), the most extensively investigated member of a channel-forming protein family, is able to form pores conducting molecules up to 1.5 kDa, like ATP, upon activation. In the olfactory epithelium (OE), ATP modulates olfactory responsiveness and plays a role in proliferation and differentiation of olfactory sensory neurons (OSNs). This process continuously takes place in the OE, as neurons are replaced throughout the whole lifespan. The recent discovery of Panx1 expression in the OE raises the question whether Panx1 mediates ATP release responsible for modulating chemosensory function. In this study, we analyzed pannexin expression in the OE and a possible role of Panx1 in olfactory function using a Panx1−/− mouse line with a global ablation of Panx1. This mouse model has been previously used to investigate Panx1 functions in the retina and adult hippocampus. Here, qPCR, in-situ hybridization, and immunohistochemistry (IHC) demonstrated that Panx1 is expressed in axon bundles deriving from sensory neurons of the OE. The localization, distribution, and expression of major olfactory signal transduction proteins were not significantly altered in Panx1−/− mice. Further, functional analysis of Panx1−/− animals does not reveal any major impairment in odor perception, indicated by electroolfactogram (EOG) measurements and behavioral testing. However, ATP release evoked by potassium gluconate application was reduced in Panx1−/− mice. This result is consistent with previous reports on ATP release in isolated erythrocytes and spinal or lumbar cord preparations from Panx1−/− mice, suggesting that Panx1 is one of several alternative pathways to release ATP in the olfactory system.

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Section: Introductionmentioning

confidence: 80%

Investigation of olfactory function in a Panx1 knock out mouse model

Kurtenbach

Whyte-Fagundes

Gelis

et al. 2014

Front. Cell. Neurosci.

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“…For instance, it is interesting to see that drPanx1a is less sensitive to ATP. Recently, evidence has been obtained that retinal horizontal cells release ATP via drPanx1a channels [34]. ATP is hydrolyzed extracellularly leading to acidification of the synaptic cleft.…”

Section: Discussionmentioning

confidence: 99%

“…The observed pH dependent channel properties of Panx1 are of particular interest, since physiological pH changes are linked to processes such as development [41], neuronal activity [42,43], lateral inhibition in the outer retina [34,44,45] and the circadian clock [46]. Furthermore, pH-changes are highly relevant for pathological conditions like ischemia and epilepsy in vivo [47], and in experimental model systems [48,49].…”

Section: Discussionmentioning

confidence: 99%

Pannexin1 Channel Proteins in the Zebrafish Retina Have Shared and Unique Properties

et al. 2013

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In mammals, a single pannexin1 gene (Panx1) is widely expressed in the CNS including the inner and outer retinae, forming large-pore voltage-gated membrane channels, which are involved in calcium and ATP signaling. Previously, we discovered that zebrafish lack Panx1 expression in the inner retina, with drPanx1a exclusively expressed in horizontal cells of the outer retina. Here, we characterize a second drPanx1 protein, drPanx1b, generated by whole-genome duplications during teleost evolution. Homology searches strongly support the presence of pannexin sequences in cartilaginous fish and provide evidence that pannexins evolved when urochordata and chordata evolution split. Further, we confirm Panx1 ohnologs being solely present in teleosts. A hallmark of differential expression of drPanx1a and drPanx1b in various zebrafish brain areas is the non-overlapping protein localization of drPanx1a in the outer and drPanx1b in the inner fish retina. A functional comparison of the evolutionary distant fish and mouse Panx1s revealed both, preserved and unique properties. Preserved functions are the capability to form channels opening at resting potential, which are sensitive to known gap junction and hemichannel blockers, intracellular calcium, extracellular ATP and pH changes. However, drPanx1b is unique due to its highly complex glycosylation pattern and distinct electrophysiological gating kinetics. The existence of two Panx1 proteins in zebrafish displaying distinct tissue distribution, protein modification and electrophysiological properties, suggests that both proteins fulfill different functions in vivo.

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“…Support for this hypothesis comes from studies of the mammalian retina in which HEPES, a strong proton buffer, was used to disrupt surround inhibition generated in the outer retina and from a recent study in which a genetically encoded pH indicator was expressed in zebrafish cones (Davenport et al 2008, Wang et al 2014). The second hypothesis is that hemichannels (i.e., pores formed by connexins—gap junction subunits—expressed only in the horizontal cell membrane) encourage current flow through the synaptic cleft in such a way as to hyperpolarize photoreceptors when horizontal cells depolarize (Thoreson & Mangel 2012, Vroman et al 2014). …”

Section: Lateral Inhibition Modifies Signaling By Vertical Excitatorymentioning

confidence: 99%

Functional Circuitry of the Retina

Demb

Singer

2015

Annu. Rev. Vis. Sci.

167

131

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The mammalian retina is an important model system for studying neural circuitry: Its role in sensation is clear, its cell types are relatively well defined, and its responses to natural stimuli—light patterns—can be studied in vitro. To solve the retina, we need to understand how the circuits pre-synaptic to its output neurons, ganglion cells, divide the visual scene into parallel representations to be assembled and interpreted by the brain. This requires identifying the component interneurons and understanding how their intrinsic properties and synapses generate circuit behaviors. Because the cellular composition and fundamental properties of the retina are shared across species, basic mechanisms studied in the genetically modifiable mouse retina apply to primate vision. We propose that the apparent complexity of retinal computation derives from a straightforward mechanism—a dynamic balance of synaptic excitation and inhibition regulated by use-dependent synaptic depression—applied differentially to the parallel pathways that feed ganglion cells.

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Extracellular ATP Hydrolysis Inhibits Synaptic Transmission by Increasing pH Buffering in the Synaptic Cleft

Abstract: A slow mechanism of retinal synaptic inhibition involves hydrolysis of ATP released from pannexin 1 channels (from the tips of horizontal cell dendrites); the resulting protons and phosphates acidify the synaptic cleft, which inhibits neurotransmitter release.

Cited by 76 publications

References 67 publications

Investigation of olfactory function in a Panx1 knock out mouse model

Investigation of olfactory function in a Panx1 knock out mouse model

Pannexin1 Channel Proteins in the Zebrafish Retina Have Shared and Unique Properties

Functional Circuitry of the Retina

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