The ATP required for potentiation of skeletal muscle contraction is released via pannexin hemichannels

Riquelme, Manuel A.; Luis, A.; Vega, José Luis; Borić, Mauricio P.; Monyer, Hannah; Bennett, Michael V. L.; Frank, Marina; Willecke, Klaus; Sáez, Juan C.

doi:10.1016/j.neuropharm.2013.03.022

Cited by 91 publications

(102 citation statements)

References 51 publications

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“…Consistent with this assertion, monocytes express several P2 receptors that selectively recognize nucleotides. Even though all of them respond to ATP, P2Y 2 and P2Y 4 have high affinity for UTP; P2Y 6 , and P2Y 8 have high affinity for UDP; and P2Y 1 , P1Y 12 , and P2Y 13 have high affinity for ADP (29). As two broadspectrum nonselective antagonists of the P2 receptors, suramin and PPADS, reduced the CM-PA-induced monocyte attraction, it is conceivable that nucleotides released by PA-challenged myotubes enact chemoattracting activity by activating one or more P2X/P2Y receptors on monocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Skeletal muscle secretes several cytokines, recently renamed "myokines" (6), but the specific soluble mediators, channels, and receptors involved in the crosstalk between skeletal muscle and immune cells are virtually undefined. Interestingly, in addition to myokines, selective stimuli induce the release of small molecules from muscle, such as prostanoids, lactate, and nucleotides (7)(8)(9)(10)(11)(12). The mechanism of release of these small molecules is unclear, but likely occurs through channels expressed at the plasma membrane.…”

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confidence: 99%

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Nucleotides Released From Palmitate-Challenged Muscle Cells Through Pannexin-3 Attract Monocytes

Pillon

Fink

et al. 2014

Diabetes

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Obesity-associated low-grade inflammation in metabolically relevant tissues contributes to insulin resistance. We recently reported monocyte/macrophage infiltration in mouse and human skeletal muscles. However, the molecular triggers of this infiltration are unknown, and the role of muscle cells in this context is poorly understood. Animal studies are not amenable to the specific investigation of this vectorial cellular communication. Using cell cultures, we investigated the crosstalk between myotubes and monocytes exposed to physiological levels of saturated and unsaturated fatty acids. Media from L6 myotubes treated with palmitate—but not palmitoleate—induced THP1 monocyte migration across transwells. Palmitate activated the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in myotubes and elevated cytokine expression, but the monocyte chemoattracting agent was not a polypeptide. Instead, nucleotide degradation eliminated the chemoattracting properties of the myotube-conditioned media. Moreover, palmitate-induced expression and activity of pannexin-3 channels in myotubes were mediated by TLR4-NF-κB, and TLR4-NF-κB inhibition or pannexin-3 knockdown prevented monocyte chemoattraction. In mice, the expression of pannexin channels increased in adipose tissue and skeletal muscle in response to high-fat feeding. These findings identify pannexins as new targets of saturated fatty acid–induced inflammation in myotubes, and point to nucleotides as possible mediators of immune cell chemoattraction toward muscle in the context of obesity.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Nucleotides Released From Palmitate-Challenged Muscle Cells Through Pannexin-3 Attract Monocytes

Pillon

Fink

et al. 2014

Diabetes

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“…18 More recently, during skeletal muscle potentiation, release of ATP through Panx1 channels was shown to be accompanied by increased serine and threonine phosphorylation, although specific phosphorylated residues were not identified. 19 Altogether, these data demonstrate the importance of Panx1 cytoplasmic domains and the need to further elucidate the mechanism of pore closure. In this study, we used a combination of structural prediction tools and circular dichroism (CD) to characterize the cytosolic domains of mPanx1.…”

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confidence: 84%

Structural order in Pannexin 1 cytoplasmic domains

2014

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“…Normal adult muscles express Panx1, but not Panx2 or Panx3 [5,22,45]. Panx1 has been localized in transverse T-tubules, where it resides next to dihidropyridine receptors [5] (Fig.…”

Section: Connexin-based Channels In Myogenesismentioning

confidence: 99%

“…HCs connect the intracellular and extracellular compartments, allowing the diffusional passage of ions and small molecules, including ATP and glucose [21,22]. Although numerous studies indicate that Panx1 HCs are permeable to ATP, these findings have been challenged by Ramanov and group, who described that Panx1 transfected in three different cell lines yields outward rectifying anion channels with negligible permeability to anions exceeding 250 Da, thus excluding ATP.…”

Section: Pannexin Hemichannels In Striate Muscle Ontogenymentioning

confidence: 99%

Regulation of pannexin and connexin channels and their functional role in skeletal muscles

Sáez

Cisterna

Vargas

et al. 2015

Cell. Mol. Life Sci.

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Myogenic precursor cells express connexins (Cx) and pannexins (Panx), proteins that form different membrane channels involved in cell-cell communication. Cx channels connect either the cytoplasm of adjacent cells, called gap junction channels (GJC), or link the cytoplasm with the extracellular space, termed hemichannels (HC), while Panx channels only support the latter. In myoblasts, Panx1 HCs play a critical role in myogenic differentiation, and Cx GJCs and possibly Cx HCs coordinate metabolic responses during later steps of myogenesis. After innervation, myofibers do not express Cxs, but still express Panx1. In myotubes and innervated myofibers, Panx1 HCs allow release of adenosine triphosphate and thus they might be involved in skeletal muscle plasticity. In addition, Panx1 HCs present in adult myofibers mediate adenosine triphosphate release and glucose uptake required for potentiation of muscle contraction. Under pathological conditions, such as upon denervation and spinal cord injury, levels of Panx1 are upregulated. However, Panx1(-/-) mice show similar degree of atrophy as denervated wild-type muscles. Skeletal muscles also express Cx HCs in the sarcolemma after denervation or spinal cord injury, plus other non-selective membrane channels, including purinergic P2X7 receptors and transient receptor potential type V2 channels. The absence of Cx43 and Cx45 is sufficient to drastically reduce denervation atrophy. Moreover, inflammatory cytokines also induce the expression of Cxs in myofibers, suggesting the expression of these Cxs as a common factor for myofiber degeneration under diverse pathological conditions. Inhibitors of skeletal muscle Cx HCs could be promising tools to prevent muscle wasting induced by conditions associated with synaptic dysfunction and inflammation.

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The ATP required for potentiation of skeletal muscle contraction is released via pannexin hemichannels

Cited by 91 publications

References 51 publications

Nucleotides Released From Palmitate-Challenged Muscle Cells Through Pannexin-3 Attract Monocytes

Nucleotides Released From Palmitate-Challenged Muscle Cells Through Pannexin-3 Attract Monocytes

Structural order in Pannexin 1 cytoplasmic domains

Regulation of pannexin and connexin channels and their functional role in skeletal muscles

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