Pannexin membrane channels are mechanosensitive conduits for ATP

Li, Bao; Locovei, Silviu; Dahl, Gerhard

doi:10.1016/j.febslet.2004.07.009

Cited by 748 publications

(907 citation statements)

References 28 publications

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“…This raises the question of how ATP is released. Pannexin1 is expressed in human RBCs and has recently been suggested to operate as the ATP release channel in erythrocytes [12,28,29]. To assess the effect of pannexin 1 on ATP release, carbenoxolone and mefloquine were used as antagonists for pannexin 1 [30,31].…”

Section: Resultsmentioning

confidence: 99%

Hemolysis in human erythrocytes by Clostridium perfringens epsilon toxin requires activation of P2 receptors

et al. 2018

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Epsilon-toxin (ETX) is produced by types B and D strains of Clostridium perfringens, which cause fatal enterotoxaemia in sheep, goats and cattle. Previous studies showed that only a restricted number of cell lines are sensitive to ETX and ETX-induced hemolysis has not previously been reported. In this study, the hemolytic ability of ETX was examined using erythrocytes from 10 species including murine, rabbit, sheep, monkey and human. We found that ETX caused hemolysis in human erythrocytes (HC50 = 0.2 μM) but not erythrocytes from the other test species. Moreover, the mechanism of ETX-induced hemolysis was further explored. Recent studies showed that some bacterial toxins induce hemolysis through purinergic receptor (P2) activation. Hence, the function of purinergic receptors in ETX-induced hemolysis was tested, and we found that the non-selective P2 receptor antagonists PPADS inhibited ETX-induced lysis of human erythrocytes in a concentration-dependent manner, indicating that ETX-induced hemolysis requires activation of purinergic receptors. P2 receptors comprise seven P2X (P2X1–7) and eight P2Y (P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11–P2Y14) receptor subtypes. The pattern of responsiveness to more selective P2-antagonists implies that both P2Y13 and P2X7 receptors are involved in ETX-induced hemolysis in human species. Furthermore, we demonstrated that extracellular ATP is likely not involved in ETX-induced hemolysis and the activation of P2 receptors. These findings clarified the mechanism of ETX-induced hemolysis and provided new insight into the activities and ETX mode of action.

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Section: Resultsmentioning

confidence: 99%

Hemolysis in human erythrocytes by Clostridium perfringens epsilon toxin requires activation of P2 receptors

et al. 2018

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“…This model makes several other predictions that will be tested in the context of left-right patterning in the future, because the amount and distribution of serotonin, gap junctions, and ion transporters can be experimentally varied in this system. However, the analysis presented here can be used to model many other signaling systems in addition to serotonin; for example, other small molecules such as cAMP, ATP, and so on are known to pass through gap junctions (Cotrina et al, 1998(Cotrina et al, , 2000Braet et al, 2003;Bao et al, 2004) and have been suggested as candidate morphogens participating in the establishment of positional information (Schiffmann, 1989(Schiffmann, , 1991.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, invertebrate gap junctions are made of innexins, a family formerly called OPUS (Barnes, 1994). A variety of small molecules and metabolites are thought to permeate gap junctional paths, including cAMP (Burnside and Collas, 2002;Webb et al, 2002;Bedner et al, 2003), ATP (Bao et al, 2004;Pearson et al, 2005), and Ca ϩϩ (Toyofuku et al, 1998;Blomstrand et al, 1999;Paemeleire et al, 2000).…”

Section: Gap Junctional Signalingmentioning

confidence: 99%

Mathematical model of morphogen electrophoresis through gap junctions

Esser

Smith

Weaver

et al. 2006

Developmental Dynamics

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Gap junctional communication is important for embryonic morphogenesis. However, the factors regulating the spatial properties of small molecule signal flows through gap junctions remain poorly understood. Recent data on gap junctions, ion transporters, and serotonin during left-right patterning suggest a specific model: the net unidirectional transfer of small molecules through long-range gap junctional paths driven by an electrophoretic mechanism. However, this concept has only been discussed qualitatively, and it is not known whether such a mechanism can actually establish a gradient within physiological constraints. We review the existing functional data and develop a mathematical model of the flow of serotonin through the early Xenopus embryo under an electrophoretic force generated by ion pumps. Through computer simulation of this process using realistic parameters, we explored quantitatively the dynamics of morphogen movement through gap junctions, confirming the plausibility of the proposed electrophoretic mechanism, which generates a considerable gradient in the available time frame. The model made several testable predictions and revealed properties of robustness, cellular gradients of serotonin, and the dependence of the gradient on several developmental constants. This work quantitatively supports the plausibility of electrophoretic control of morphogen movement through gap junctions during early left-right patterning. This conceptual framework for modeling gap junctional signaling-an epigenetic patterning mechanism of wide relevance in biological regulation-suggests numerous experimental approaches in other patterning systems.

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“…Pannexins are structurally homologous to connexins and can form plasma membrane channels in Xenopus oocytes [93][94][95]. Several properties and findings make pannexin 1 a very attractive candidate for an ATP-releasing channel: (1) It can be activated by membrane depolarisation in the physiological range and allows permeation of small molecules including ATP [93][94][95]; (2) it can be activated at normal extracellular Ca 2+ concentrations [93]; (3) it is activated by mechanical perturbation [95]; (4) it may open under conditions of cellular energy depletion [96]; and (5) it can be activated by increase of intracellular Ca 2+ [95,97]. In addition, important evidence suggests that the longsought P2X 7 -related pore structure may be pannexin 1 [98,99].…”

Section: A Link To Connexins Pannexins and Atp-permeable Hemichannelsmentioning

confidence: 99%

ATP release from non-excitable cells

Praetorius

Leipziger

2009

Purinergic Signalling

207

229

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All cells release nucleotides and are in one way or another involved in local autocrine and paracrine regulation of organ function via stimulation of purinergic receptors. Significant technical advances have been made in recent years to quantify more precisely resting and stimulated adenosine triphosphate (ATP) concentrations in close proximity to the plasma membrane. These technical advances are reviewed here. However, the mechanisms by which cells release ATP continue to be enigmatic. The current state of knowledge on different suggested mechanisms is also reviewed. Current evidence suggests that two separate regulated modes of ATP release co-exist in nonexcitable cells: (1) a conductive pore which in several systems has been found to be the channel pannexin 1 and (2) vesicular release. Modes of stimulation of ATP release are reviewed and indicate that both subtle mechanical stimulation and agonist-triggered release play pivotal roles. The mechano-sensor for ATP release is not yet defined.

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Pannexin membrane channels are mechanosensitive conduits for ATP

Cited by 748 publications

References 28 publications

Hemolysis in human erythrocytes by Clostridium perfringens epsilon toxin requires activation of P2 receptors

Hemolysis in human erythrocytes by Clostridium perfringens epsilon toxin requires activation of P2 receptors

Mathematical model of morphogen electrophoresis through gap junctions

ATP release from non-excitable cells

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