The Experts below are selected from a list of 2487 Experts worldwide ranked by ideXlab platform
Dale W Laird - One of the best experts on this subject based on the ideXlab platform.
-
next generation connexin and Pannexin cell biology
Trends in Cell Biology, 2016Co-Authors: Jessica L Esseltine, Dale W LairdAbstract:Connexins and Pannexins are two families of large-pore channel forming proteins that are capable of passing small signaling molecules. While connexins serve the seminal task of direct gap junctional intercellular communication, Pannexins are far less understood but function primarily as single membrane channels in autocrine and paracrine signaling. Advancements in connexin and Pannexin biology in recent years has revealed that in addition to well-described classical functions at the plasma membrane, exciting new evidence suggests that connexins and Pannexins participate in alternative pathways involving multiple intracellular compartments. Here we briefly highlight classical functions of connexins and Pannexins but focus our attention mostly on the transformative findings that suggest that these channel-forming proteins may serve roles far beyond our current understandings.
-
Pannexin channels and their links to human disease
Biochemical Journal, 2014Co-Authors: Silvia Penuela, Luke Harland, Jamie Simek, Dale W LairdAbstract:In less than a decade, a small family of channel-forming glycoproteins, named Pannexins, have captured the interest of many biologists, in large part due to their association with common diseases, ranging from cancers to neuropathies to infectious diseases. Although the Pannexin family consists of only three members (Panx1, Panx2 and Panx3), one or more of these Pannexins are expressed in virtually every mammalian organ, implicating their potential role in a diverse array of pathophysiologies. Panx1 is the most extensively studied, but features of this Pannexin must be cautiously extrapolated to the other Pannexins, as for example we now know that Panx2, unlike Panx1, exhibits unique properties such as a tendency to be retained within intracellular compartments. In the present review, we assess the biochemical and channel features of Pannexins focusing on the literature which links these unique molecules to over a dozen diseases and syndromes. Although no germ-line mutations in genes encoding Pannexins have been linked to any diseases, many cases have shown that high Pannexin expression is associated with disease onset and/or progression. Disease may also occur, however, when Pannexins are underexpressed, highlighting that Pannexin expression must be exquisitely regulated. Finally, we discuss some of the most pressing questions and controversies in the Pannexin field as the community seeks to uncover the full biological relevance of Pannexins in healthy organs and during disease.
-
The biochemistry and function of Pannexin channels.
Biochimica et Biophysica Acta, 2012Co-Authors: Silvia Penuela, Ruchi Gehi, Dale W LairdAbstract:Abstract Three family members compose the Pannexin family of channel-forming glycoproteins (Panx1, Panx2 and Panx3). Their primary function is defined by their capacity to form single-membrane channels that are regulated by post-translational modifications, channel intermixing, and sub-cellular expression profiles. Panx1 is ubiquitously expressed in many mammalian tissues, while Panx2 and Panx3 appear to be more restricted in their expression. Paracrine functions of Panx1 as an ATP release channel have been extensively studied and this channel plays a key role, among others, in the release of “find-me” signals for apoptotic cell clearance. In addition Panx1 has been linked to propagation of calcium waves, regulation of vascular tone, mucociliary lung clearance, taste-bud function and has been shown to act like a tumor suppressor in gliomas. Panx1 channel opening can also be detrimental, contributing to cell death and seizures under ischemic or epileptic conditions and even facilitating HIV-1 viral infection. Panx2 is involved in differentiation of neurons while Panx3 plays a role in the differentiation of chondrocytes, osteoblasts and the maturation and transport of sperm. Using the available Panx1 knockout mouse models it has now become possible to explore some of its physiological functions. However, given the potential for one Pannexin to compensate for another it seems imperative to generate single and double knockout mouse models involving all three Pannexins and evaluate their interplay in normal differentiation and development as well as in malignant transformation and disease. This article is part of a Special Issue entitled: The communicating junctions, roles and dysfunctions.
-
Pannexin 3 is a novel target for runx2 expressed by osteoblasts and mature growth plate chondrocytes
Journal of Bone and Mineral Research, 2011Co-Authors: Stephen R Bond, Silvia Penuela, Dale W Laird, Arthur V Sampaio, Michael T Underhill, Christian C NausAbstract:Pannexins are a class of chordate channel proteins identified by their homology to insect gap junction proteins. The Pannexin family consists of three members, Panx1, Panx2, and Panx3, and the role each of these proteins plays in cellular processes is still under investigation. Previous reports of Panx3 expression indicate enrichment in skeletal tissues, so we have further investigated this distribution by surveying the developing mouse embryo with immunofluorescence. High levels of Panx3 were detected in intramembranous craniofacial flat bones, as well as long bones of the appendicular and axial skeleton. This distribution is the result of expression in both osteoblasts and hypertrophic chondrocytes. Furthermore, the Panx3 promoter contains putative binding sites for transcription factors involved in bone formation, and we show that the sequence between bases −275 and −283 is responsive to Runx2 activation. Taken together, our data suggests that Panx3 may serve an important role in bone development, and is a novel target for Runx2-dependent signaling. © 2011 American Society for Bone and Mineral Research
-
Pannexin 3 is a novel target for runx2 expressed by osteoblasts and mature growth plate chondrocytes
Journal of Bone and Mineral Research, 2011Co-Authors: Stephen R Bond, Silvia Penuela, Dale W Laird, Arthur V Sampaio, Michael T Underhill, Alice Lau, Christian C NausAbstract:Pannexins are a class of chordate channel proteins identified by their homology to insect gap junction proteins. The Pannexin family consists of three members, Panx1, Panx2, and Panx3, and the role each of these proteins plays in cellular processes is still under investigation. Previous reports of Panx3 expression indicate enrichment in skeletal tissues, so we have further investigated this distribution by surveying the developing mouse embryo with immunofluorescence. High levels of Panx3 were detected in intramembranous craniofacial flat bones, as well as long bones of the appendicular and axial skeleton. This distribution is the result of expression in both osteoblasts and hypertrophic chondrocytes. Furthermore, the Panx3 promoter contains putative binding sites for transcription factors involved in bone formation, and we show that the sequence between bases -275 and -283 is responsive to Runx2 activation. Taken together, our data suggests that Panx3 may serve an important role in bone development, and is a novel target for Runx2-dependent signaling.
Valery I Shestopalov - One of the best experts on this subject based on the ideXlab platform.
-
Pannexins are potential new players in the regulation of cerebral homeostasis during sleep wake cycle
Frontiers in Cellular Neuroscience, 2017Co-Authors: Valery I Shestopalov, Yuri V. Panchin, O S Tarasova, Dina Gaynullina, V M KovalzonAbstract:During brain homeostasis, both neurons and astroglia release ATP that is rapidly converted to adenosine in the extracellular space. Pannexin1 (Panx1) hemichannels represent a major conduit of non-vesicular ATP release from brain cells. Previous studies have shown that Panx1-/- mice possess severe disruption of the sleep-wake cycle. Here, we review experimental data supporting the involvement of Pannexins in the coordination of fundamental sleep-associated brain processes, such as neuronal activity and regulation of cerebrovascular tone. Panx1 hemichannels are likely implicated in the regulation of the sleep-wake cycle via an indirect effect of released ATP on adenosine receptors and through interaction with other somnogens, such as IL-1β, TNFα and prostaglandin D2. In addition to the recently established role of Panx1 in the regulation of endothelium-dependent arterial dilation, similar signaling pathways are the major cellular component of neurovascular coupling. The new discovered role of Pannexins in sleep regulation may have broad implications in coordinating neuronal activity and homeostatic housekeeping processes during the sleep-wake cycle.
-
sleep wakefulness cycle and behavior in Pannexin1 knockout mice
Behavioural Brain Research, 2017Co-Authors: V M Kovalzon, Valery I Shestopalov, L S Moiseenko, A V Ambaryan, Stefan Kurtenbach, Yury PanchinAbstract:Pannexins are membrane channel proteins that play a role in a number of critical biological processes (Panchin et al., 2000; Shestopalov, Panchin, 2008). Among other cellular functions, Pannexin hemichannels serve as purine nucleoside conduits providing ATP efflux into the extracellular space (Dahl, 2015), where it is rapidly degraded to adenosine. Pannexin1 (Panx1) is abundantly expressed in the brain and has been shown to contribute to adenosine signaling in nervous system tissues (Prochnow et al., 2012). We hypothesized that Pannexin1 may contribute to sleep-wake cycle regulation through extracellular adenosine, a well-established paracrine factor in slow wave sleep. To investigate this link, EEG and movement activity throughout the light/dark cycle were compared in Panx1−/− and Panx1+/+ mice. We found a significant increase in waking and a correspondent decrease in slow wave sleep percentages in the Panx1−/− animals. These changes were especially pronounced during the dark period. Furthermore, we found a significant increase in movement activity of Panx1−/− mice. These findings are consistent with the hypothesis that extracellular adenosine is relatively depleted in Panx1−/− animals due to the absence of the ATP-permeable hemichannels. At the same time, sleep rebound after a 6-h sleep deprivation remained unchanged in Panx1−/− mice as compared to the control animals. Behavioral tests revealed that Panx1−/− mice were significantly faster during their descent along the vertical pole but more sluggish during their run through the horizontal pole as compared to the control mice.
-
the role of Pannexin hemichannels in inflammation and regeneration
Frontiers in Physiology, 2014Co-Authors: Helen P Makarenkova, Valery I ShestopalovAbstract:Tissue injury involves coordinated systemic responses including inflammatory response, targeted cell migration, cell-cell communication, stem cell activation and proliferation, and tissue inflammation and regeneration. The inflammatory response is an important prerequisite for regeneration. Multiple studies suggest that extensive cell-cell communication during tissue regeneration is coordinated by purinergic signaling via extracellular adenosine triphosphate (ATP). Most recent data indicates that ATP release for such communication is mediated by hemichannels formed by connexins and Pannexins. The Pannexin family consists of three vertebrate proteins (Panx 1, 2, and 3) that have low sequence homology with other gap junction proteins and were shown to form predominantly non-junctional plasma membrane hemichannels. Pannexin-1 (Panx1) channels function as an integral component of the P2X/P2Y purinergic signaling pathway and is arguably the major contributor to pathophysiological ATP release. Panx1 is expressed in many tissues, with highest levels detected in developing brain, retina and skeletal muscles. Panx1 channel expression and activity is reported to increase significantly following injury/inflammation and during regeneration and differentiation. Recent studies also report that pharmacological blockade of the Panx1 channel or genetic ablation of the Panx1 gene cause significant disruption of progenitor cell migration, proliferation, and tissue regeneration. These findings suggest that Pannexins play important roles in activation of both post-injury inflammatory response and the subsequent process of tissue regeneration. Due to wide expression in multiple tissues and involvement in diverse signaling pathways, Pannexins and connexins are currently being considered as therapeutic targets for traumatic brain or spinal cord injuries, ischemic stroke and cancer. The precise role of Pannexins and connexins in the balance between tissue inflammation and regeneration needs to be further understood.
-
Pannexins and gap junction protein diversity
Cellular and Molecular Life Sciences, 2008Co-Authors: Valery I Shestopalov, Yu V PanchinAbstract:Gap junctions (GJs) are composed of proteins that form a channel connecting the cytoplasm of adjacent cells. Connexins were initially considered to be the only proteins capable of GJ formation. Another family of GJ proteins (innexins) were first found in invertebrates and were proposed to be renamed Pannexins after their orthologs were discovered in vertebrates. The lack of both connexins and Pannexins in the genomes of some metazoans suggests that other, still undiscovered GJ proteins exist. In vertebrates, connexins and Pannexins co-exist. Here we discuss whether vertebrate Pannexins have a nonredundant role in animal physiology. Pannexin channels appear to be suited for ATP and calcium signaling and play a role in the maintenance of calcium homeostasis by mechanisms implicating both GJ and nonjunctional function. Suggested roles in the ischemic death of neurons, schizophrenia, inflammation and tumor suppression have drawn much attention to exploring the molecular properties and cellular functions of Pannexins.
Annmarie Surprenant - One of the best experts on this subject based on the ideXlab platform.
-
the p2x7 receptor Pannexin connection to dye uptake and il 1β release
Purinergic Signalling, 2009Co-Authors: Pablo Pelegrin, Annmarie SurprenantAbstract:The P2X7 receptor (P2X7R) is uniquely associated with two distinct cellular responses: activation of a dye-permeable pathway allowing passage of molecules up to 900 Da and rapid release of the pro-inflammatory cytokine, interleukin-1β (IL-1β), from activated macrophage. How this dye uptake path forms and whether it is involved in IL-1β release has not been known. Pannexin-1 is a recently identified protein found to physically associate with the P2X7R. Inhibition of Pannexin-1 does not alter P2X7R ion channel activation or associated calcium flux but blocks one component of P2X7R-induced dye uptake and unmasks a slower, previously undetected, dye uptake pathway. Inhibition of Pannexin-1 blocks P2X7R-mediated IL-1β release from macrophage as well as release mediated by other stimuli which couple to activation of capase-1 and additionally inhibits the release of interleukin-1α, a member of the IL-1 family whose processing does not require caspase-1 activation. Thus, Pannexin-1 is linked to both dye uptake and IL-1β release but via distinct mechanisms.
-
Pannexin 1 couples to maitotoxin and nigericin induced interleukin 1β release through a dye uptake independent pathway
Journal of Biological Chemistry, 2007Co-Authors: Pablo Pelegrin, Annmarie SurprenantAbstract:Abstract Pannexin-1 is a recently identified membrane protein that can act as a nonselective pore permeable to dyes such as ethidium when ectopically expressed. Blockade of Pannexin-1 in macrophage endogenously expressing the ATP-gated P2X7 receptor (P2X7R) blocks the initial dye uptake, but not the ionic current, and also blocks processing and release of interleukin-1β (IL-1β) in response to P2X7R activation. These results suggest that Pannexin-1 may be a hemichannel activated by the P2X7R to provide the conduit for dye uptake and downstream signaling to processing and release of IL-1β. We have pursued this hypothesis by measuring dye uptake and IL-1β processing and release in mouse J774 macrophage in response to P2X7R activation and to maitotoxin and nigericin, two agents considered to evoke IL-1β release via the same mechanism. The experiments were carried out over time periods during which no lactate dehydrogenase was released from cells to examine only noncytolytic pathways. P2X7R activation evoked dye uptake that could be separated into two components by Pannexin-1 inhibition: an initial rapid phase and a slower Pannexin-1-independent phase. Maitotoxin-evoked dye uptake was unaltered by Pannexin-1 inhibition. Nigericin did not induce dye uptake. Inhibition of Pannexin-1 blocked caspase-1 and IL-1β processing and release in response to all three stimuli. Thus, although Pannexin-1 is required for IL-1β release in response to maitotoxin, nigericin, and ATP, a mechanism distinct from Pannexin-1 hemichannel activation must underlie the former two processes.
Silvia Penuela - One of the best experts on this subject based on the ideXlab platform.
-
Pannexin 1 binds β catenin to modulate melanoma cell growth and metabolism
Journal of Biological Chemistry, 2021Co-Authors: Samar Sayedyahossein, Kenneth Huang, Christopher Zhang, Alexandra M Kozlov, Danielle Johnston, Daniel Nourinejad, Lina Dagnino, Dean H Betts, David B Sacks, Silvia PenuelaAbstract:Melanoma is the most aggressive skin malignancy with increasing incidence worldwide. Pannexin1 (PANX1), a member of the Pannexin family of channel-forming glycoproteins, regulates cellular processes in melanoma cells including proliferation, migration, and invasion/metastasis. However, the mechanisms responsible for coordinating and regulating PANX1 function remain unclear. Here, we demonstrated a direct interaction between the C-terminal region of PANX1 and the N-terminal portion of β-catenin, a key transcription factor in the Wnt pathway. At the protein level, β-catenin was significantly decreased when PANX1 was either knocked down or inhibited by two PANX1 blockers, Probenecid and Spironolactone. Immunofluorescence imaging showed a disrupted pattern of β-catenin localization at the cell membrane in PANX1-deficient cells, and transcription of several Wnt target genes, including MITF, was suppressed. In addition, a mitochondrial stress test revealed that the metabolism of PANX1-deficient cells was impaired, indicating a role for PANX1 in the regulation of the melanoma cell metabolic profile. Taken together, our data show that PANX1 directly interacts with β-catenin to modulate growth and metabolism in melanoma cells. These findings provide mechanistic insight into PANX1-mediated melanoma progression and may be applicable to other contexts where PANX1 and β-catenin interact as a potential new component of the Wnt signaling pathway.
-
Pannexin 1 and Pannexin 3 channels regulate skeletal muscle myoblast proliferation and differentiation
Journal of Biological Chemistry, 2014Co-Authors: Stephanie Langlois, Silvia Penuela, Kyle N Cowan, Bryce Cowan, Xiao Xiang, Kelsey YoungAbstract:Abstract Pannexins constitute a family of three glycoproteins (Panx1, 2, and 3) forming single membrane channels. Recent work demonstrated that Panx1 is expressed in skeletal muscle and involved in the potentiation of contraction. However, Panxs functions in skeletal muscle cell differentiation and proliferation had yet to be assessed. We show here that Panx1 and Panx3, but not Panx2, are present in human and rodent skeletal muscle, and their various species are differentially expressed in fetal versus adult human skeletal muscle tissue. Panx1 levels were very low in undifferentiated human primary skeletal muscle cells (SkMC) and myoblasts (HSMM), but increased drastically during differentiation and became the main Panx expressed in differentiated cells. Using HSMM, we found that Panx1 expression promotes this process, whereas it was impaired in the presence of probenecid or carbenoxolone. As for Panx3, its lower molecular weight species were prominent in adult skeletal muscle, but very low in the fetal tissue and in undifferentiated skeletal muscle cells and myoblasts. Its over-expression (∼43 kDa species) induced HSMM differentiation and also inhibited their proliferation. On the other hand, a ∼70 kDa immunoreactive species of Panx3, likely glycosylated, sialylated, and phosphorylated, was highly expressed in proliferative myoblasts but strikingly down-regulated during their differentiation. Reduction of its endogenous expression using two Panx3 shRNAs significantly inhibited HSMM proliferation, without triggering their differentiation. In summary, our results demonstrate that Panx1 and Panx3 are co-expressed in human skeletal muscle myoblasts and play a pivotal role in dictating the proliferation and differentiation status of these cells.
-
Pannexin channels and their links to human disease
Biochemical Journal, 2014Co-Authors: Silvia Penuela, Luke Harland, Jamie Simek, Dale W LairdAbstract:In less than a decade, a small family of channel-forming glycoproteins, named Pannexins, have captured the interest of many biologists, in large part due to their association with common diseases, ranging from cancers to neuropathies to infectious diseases. Although the Pannexin family consists of only three members (Panx1, Panx2 and Panx3), one or more of these Pannexins are expressed in virtually every mammalian organ, implicating their potential role in a diverse array of pathophysiologies. Panx1 is the most extensively studied, but features of this Pannexin must be cautiously extrapolated to the other Pannexins, as for example we now know that Panx2, unlike Panx1, exhibits unique properties such as a tendency to be retained within intracellular compartments. In the present review, we assess the biochemical and channel features of Pannexins focusing on the literature which links these unique molecules to over a dozen diseases and syndromes. Although no germ-line mutations in genes encoding Pannexins have been linked to any diseases, many cases have shown that high Pannexin expression is associated with disease onset and/or progression. Disease may also occur, however, when Pannexins are underexpressed, highlighting that Pannexin expression must be exquisitely regulated. Finally, we discuss some of the most pressing questions and controversies in the Pannexin field as the community seeks to uncover the full biological relevance of Pannexins in healthy organs and during disease.
-
The biochemistry and function of Pannexin channels.
Biochimica et Biophysica Acta, 2012Co-Authors: Silvia Penuela, Ruchi Gehi, Dale W LairdAbstract:Abstract Three family members compose the Pannexin family of channel-forming glycoproteins (Panx1, Panx2 and Panx3). Their primary function is defined by their capacity to form single-membrane channels that are regulated by post-translational modifications, channel intermixing, and sub-cellular expression profiles. Panx1 is ubiquitously expressed in many mammalian tissues, while Panx2 and Panx3 appear to be more restricted in their expression. Paracrine functions of Panx1 as an ATP release channel have been extensively studied and this channel plays a key role, among others, in the release of “find-me” signals for apoptotic cell clearance. In addition Panx1 has been linked to propagation of calcium waves, regulation of vascular tone, mucociliary lung clearance, taste-bud function and has been shown to act like a tumor suppressor in gliomas. Panx1 channel opening can also be detrimental, contributing to cell death and seizures under ischemic or epileptic conditions and even facilitating HIV-1 viral infection. Panx2 is involved in differentiation of neurons while Panx3 plays a role in the differentiation of chondrocytes, osteoblasts and the maturation and transport of sperm. Using the available Panx1 knockout mouse models it has now become possible to explore some of its physiological functions. However, given the potential for one Pannexin to compensate for another it seems imperative to generate single and double knockout mouse models involving all three Pannexins and evaluate their interplay in normal differentiation and development as well as in malignant transformation and disease. This article is part of a Special Issue entitled: The communicating junctions, roles and dysfunctions.
-
Pannexin 3 is a novel target for runx2 expressed by osteoblasts and mature growth plate chondrocytes
Journal of Bone and Mineral Research, 2011Co-Authors: Stephen R Bond, Silvia Penuela, Dale W Laird, Arthur V Sampaio, Michael T Underhill, Christian C NausAbstract:Pannexins are a class of chordate channel proteins identified by their homology to insect gap junction proteins. The Pannexin family consists of three members, Panx1, Panx2, and Panx3, and the role each of these proteins plays in cellular processes is still under investigation. Previous reports of Panx3 expression indicate enrichment in skeletal tissues, so we have further investigated this distribution by surveying the developing mouse embryo with immunofluorescence. High levels of Panx3 were detected in intramembranous craniofacial flat bones, as well as long bones of the appendicular and axial skeleton. This distribution is the result of expression in both osteoblasts and hypertrophic chondrocytes. Furthermore, the Panx3 promoter contains putative binding sites for transcription factors involved in bone formation, and we show that the sequence between bases −275 and −283 is responsive to Runx2 activation. Taken together, our data suggests that Panx3 may serve an important role in bone development, and is a novel target for Runx2-dependent signaling. © 2011 American Society for Bone and Mineral Research
V M Kovalzon - One of the best experts on this subject based on the ideXlab platform.
-
Pannexins are potential new players in the regulation of cerebral homeostasis during sleep wake cycle
Frontiers in Cellular Neuroscience, 2017Co-Authors: Valery I Shestopalov, Yuri V. Panchin, O S Tarasova, Dina Gaynullina, V M KovalzonAbstract:During brain homeostasis, both neurons and astroglia release ATP that is rapidly converted to adenosine in the extracellular space. Pannexin1 (Panx1) hemichannels represent a major conduit of non-vesicular ATP release from brain cells. Previous studies have shown that Panx1-/- mice possess severe disruption of the sleep-wake cycle. Here, we review experimental data supporting the involvement of Pannexins in the coordination of fundamental sleep-associated brain processes, such as neuronal activity and regulation of cerebrovascular tone. Panx1 hemichannels are likely implicated in the regulation of the sleep-wake cycle via an indirect effect of released ATP on adenosine receptors and through interaction with other somnogens, such as IL-1β, TNFα and prostaglandin D2. In addition to the recently established role of Panx1 in the regulation of endothelium-dependent arterial dilation, similar signaling pathways are the major cellular component of neurovascular coupling. The new discovered role of Pannexins in sleep regulation may have broad implications in coordinating neuronal activity and homeostatic housekeeping processes during the sleep-wake cycle.
-
sleep wakefulness cycle and behavior in Pannexin1 knockout mice
Behavioural Brain Research, 2017Co-Authors: V M Kovalzon, Valery I Shestopalov, L S Moiseenko, A V Ambaryan, Stefan Kurtenbach, Yury PanchinAbstract:Pannexins are membrane channel proteins that play a role in a number of critical biological processes (Panchin et al., 2000; Shestopalov, Panchin, 2008). Among other cellular functions, Pannexin hemichannels serve as purine nucleoside conduits providing ATP efflux into the extracellular space (Dahl, 2015), where it is rapidly degraded to adenosine. Pannexin1 (Panx1) is abundantly expressed in the brain and has been shown to contribute to adenosine signaling in nervous system tissues (Prochnow et al., 2012). We hypothesized that Pannexin1 may contribute to sleep-wake cycle regulation through extracellular adenosine, a well-established paracrine factor in slow wave sleep. To investigate this link, EEG and movement activity throughout the light/dark cycle were compared in Panx1−/− and Panx1+/+ mice. We found a significant increase in waking and a correspondent decrease in slow wave sleep percentages in the Panx1−/− animals. These changes were especially pronounced during the dark period. Furthermore, we found a significant increase in movement activity of Panx1−/− mice. These findings are consistent with the hypothesis that extracellular adenosine is relatively depleted in Panx1−/− animals due to the absence of the ATP-permeable hemichannels. At the same time, sleep rebound after a 6-h sleep deprivation remained unchanged in Panx1−/− mice as compared to the control animals. Behavioral tests revealed that Panx1−/− mice were significantly faster during their descent along the vertical pole but more sluggish during their run through the horizontal pole as compared to the control mice.
