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Pannexin-1 as a potentiator of ligand-gated receptor signaling.

Isakson BE, Thompson RJ - Channels (Austin) (2014)

Bottom Line: Although similar in secondary structure to the connexins, pannexins notably do not form endogenous gap junctions and act as bona fide ion channels.There is an intriguing theme with pannexins that has begun to develop.Although the literature remains sparse, this emerging concept appears consistent between both ionotropic and metabotropic receptors of several ligand families.

View Article: PubMed Central - PubMed

Affiliation: Robert M. Berne Cardiovascular Research Center; University of Virginia School of Medicine; Charlottesville, VA USA; Department of Molecular Physiology and Biophysics; University of Virginia School of Medicine; Charlottesville, VA USA.

ABSTRACT
Pannexins are a class of plasma membrane spanning proteins that presumably form a hexameric, non-selective ion channel. Although similar in secondary structure to the connexins, pannexins notably do not form endogenous gap junctions and act as bona fide ion channels. The pannexins have been primarily studied as ATP-release channels, but the overall diversity of their functions is still being elucidated. There is an intriguing theme with pannexins that has begun to develop. In this review we analyze several recent reports that converge on the idea that pannexin channels (namely Panx1) can potentiate ligand-gated receptor signaling. Although the literature remains sparse, this emerging concept appears consistent between both ionotropic and metabotropic receptors of several ligand families.

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Figure 1. Expression of Panx1 and Cx43 with α1-AR in mesenteric arterioles. Frozen sections of third-order mouse mesenteric arterioles were viewed transverse via confocal microscopy. Magenta is autofluorescence of the internal elastic lamina (IEL) separating endothelial cells (EC) from smooth muscle cells (SMC), green (goat anti-rabbit Cy5) is the α1-AR, and red (goat anti-rabbit Alexa 594) is either Cx43 (top) or Panx1 (bottom). Note the extensive colocalization between Panx1 and α1-AR in smooth muscle, but the lack of association between Cx43 and α1-AR. Scale bar is 20 μm. Immunocytochemistry was performed as described and all antibodies have previously been extensively verified.16, 41
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Figure 1: Figure 1. Expression of Panx1 and Cx43 with α1-AR in mesenteric arterioles. Frozen sections of third-order mouse mesenteric arterioles were viewed transverse via confocal microscopy. Magenta is autofluorescence of the internal elastic lamina (IEL) separating endothelial cells (EC) from smooth muscle cells (SMC), green (goat anti-rabbit Cy5) is the α1-AR, and red (goat anti-rabbit Alexa 594) is either Cx43 (top) or Panx1 (bottom). Note the extensive colocalization between Panx1 and α1-AR in smooth muscle, but the lack of association between Cx43 and α1-AR. Scale bar is 20 μm. Immunocytochemistry was performed as described and all antibodies have previously been extensively verified.16, 41

Mentions: There is now accumulating evidence that pannexin channels, in particular Panx1, can serve to enhance metabotropic based signaling events. For instance, a macromolecular protein association between Panx1 and α-adrenergic receptors (AR) has been demonstrated in 2 independent reports.16,40 Some of the most interesting sets of data reknogarding an interaction between Panx1 and α1–AR comes from the over- or under-expression of Panx1 specifically in smooth muscle cells from intact resistance arteries.16 In these experiments, the more Panx1 in smooth muscle cells (with plasmid transfection) caused increased constriction in response to phenylephrine, whereas as siRNA of Panx1 in smooth muscle cells caused a decreased constriction in response to phenylephrine. There was no discernable change in the expression of the α1–AR. This observation bodes well with an in-depth study of pannexin channel expression that found only the Panx1 isoform was expressed in smooth muscle cells of resistance arteries (e.g., thoracodorsal arteries, mesenteric arteries (Fig. 1) and numerous other arterioles), whereas it was completely absent from conduit arteries.41 The important extrapolation from this data are that possibly the amount of Panx1 in the smooth muscle of resistance arteries is important for the regulation of peripheral resistance (at least the sympathetic nerve component), and thus overall blood pressure.


Pannexin-1 as a potentiator of ligand-gated receptor signaling.

Isakson BE, Thompson RJ - Channels (Austin) (2014)

Figure 1. Expression of Panx1 and Cx43 with α1-AR in mesenteric arterioles. Frozen sections of third-order mouse mesenteric arterioles were viewed transverse via confocal microscopy. Magenta is autofluorescence of the internal elastic lamina (IEL) separating endothelial cells (EC) from smooth muscle cells (SMC), green (goat anti-rabbit Cy5) is the α1-AR, and red (goat anti-rabbit Alexa 594) is either Cx43 (top) or Panx1 (bottom). Note the extensive colocalization between Panx1 and α1-AR in smooth muscle, but the lack of association between Cx43 and α1-AR. Scale bar is 20 μm. Immunocytochemistry was performed as described and all antibodies have previously been extensively verified.16, 41
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 1: Figure 1. Expression of Panx1 and Cx43 with α1-AR in mesenteric arterioles. Frozen sections of third-order mouse mesenteric arterioles were viewed transverse via confocal microscopy. Magenta is autofluorescence of the internal elastic lamina (IEL) separating endothelial cells (EC) from smooth muscle cells (SMC), green (goat anti-rabbit Cy5) is the α1-AR, and red (goat anti-rabbit Alexa 594) is either Cx43 (top) or Panx1 (bottom). Note the extensive colocalization between Panx1 and α1-AR in smooth muscle, but the lack of association between Cx43 and α1-AR. Scale bar is 20 μm. Immunocytochemistry was performed as described and all antibodies have previously been extensively verified.16, 41
Mentions: There is now accumulating evidence that pannexin channels, in particular Panx1, can serve to enhance metabotropic based signaling events. For instance, a macromolecular protein association between Panx1 and α-adrenergic receptors (AR) has been demonstrated in 2 independent reports.16,40 Some of the most interesting sets of data reknogarding an interaction between Panx1 and α1–AR comes from the over- or under-expression of Panx1 specifically in smooth muscle cells from intact resistance arteries.16 In these experiments, the more Panx1 in smooth muscle cells (with plasmid transfection) caused increased constriction in response to phenylephrine, whereas as siRNA of Panx1 in smooth muscle cells caused a decreased constriction in response to phenylephrine. There was no discernable change in the expression of the α1–AR. This observation bodes well with an in-depth study of pannexin channel expression that found only the Panx1 isoform was expressed in smooth muscle cells of resistance arteries (e.g., thoracodorsal arteries, mesenteric arteries (Fig. 1) and numerous other arterioles), whereas it was completely absent from conduit arteries.41 The important extrapolation from this data are that possibly the amount of Panx1 in the smooth muscle of resistance arteries is important for the regulation of peripheral resistance (at least the sympathetic nerve component), and thus overall blood pressure.

Bottom Line: Although similar in secondary structure to the connexins, pannexins notably do not form endogenous gap junctions and act as bona fide ion channels.There is an intriguing theme with pannexins that has begun to develop.Although the literature remains sparse, this emerging concept appears consistent between both ionotropic and metabotropic receptors of several ligand families.

View Article: PubMed Central - PubMed

Affiliation: Robert M. Berne Cardiovascular Research Center; University of Virginia School of Medicine; Charlottesville, VA USA; Department of Molecular Physiology and Biophysics; University of Virginia School of Medicine; Charlottesville, VA USA.

ABSTRACT
Pannexins are a class of plasma membrane spanning proteins that presumably form a hexameric, non-selective ion channel. Although similar in secondary structure to the connexins, pannexins notably do not form endogenous gap junctions and act as bona fide ion channels. The pannexins have been primarily studied as ATP-release channels, but the overall diversity of their functions is still being elucidated. There is an intriguing theme with pannexins that has begun to develop. In this review we analyze several recent reports that converge on the idea that pannexin channels (namely Panx1) can potentiate ligand-gated receptor signaling. Although the literature remains sparse, this emerging concept appears consistent between both ionotropic and metabotropic receptors of several ligand families.

Show MeSH