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CO2-sensitive connexin hemichannels in neurons and glia : three different modes of signalling?
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Hill, Emily, Dale, Nicholas and Wall, Mark J. (2021) CO2-sensitive connexin hemichannels in neurons and glia : three different modes of signalling? International Journal of Molecular Sciences, 22 (14). 7254. doi:10.3390/ijms22147254 ISSN 1422-0067.
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WRAP-CO2-sensitive-connexin-hemichannels-neurons-glia-three-different-modes-signalling-2021.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (3492Kb) | Preview |
Official URL: http://dx.doi.org/10.3390/ijms22147254
Abstract
Connexins can assemble into either gap junctions (between two cells) or hemichannels (from one cell to the extracellular space) and mediate cell-to-cell signalling. A subset of connexins (Cx26, Cx30, Cx32) are directly sensitive to CO2 and fluctuations in the level within a physiological range affect their open probability, and thus, change cell conductance. These connexins are primarily found on astrocytes or oligodendrocytes, where increased CO2 leads to ATP release, which acts on P2X and P2Y receptors of neighbouring neurons and changes excitability. CO2-sensitive hemichannels are also found on developing cortical neurons, where they play a role in producing spontaneous neuronal activity. It is plausible that the transient opening of hemichannels allows cation influx, leading to depolarisation. Recently, we have shown that dopaminergic neurons in the substantia nigra and GABAergic neurons in the VTA also express Cx26 hemichannels. An increase in the level of CO2 results in hemichannel opening, increasing whole-cell conductance, and decreasing neuronal excitability. We found that the expression of Cx26 in the dopaminergic neurons in the substantia nigra at P7-10 is transferred to glial cells by P17-21, displaying a shift from being inhibitory (to neuronal activity) in young mice, to potentially excitatory (via ATP release). Thus, Cx26 hemichannels could have three modes of signalling (release of ATP, excitatory flickering open and shut and inhibitory shunting) depending on where they are expressed (neurons or glia) and the stage of development.
| Item Type: | Journal Article | ||||||
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| Subjects: | Q Science > QD Chemistry Q Science > QP Physiology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||
| Library of Congress Subject Headings (LCSH): | Connexins, Neurons, Neuroglia, Carbon dioxide, Substantia nigra | ||||||
| Journal or Publication Title: | International Journal of Molecular Sciences | ||||||
| Publisher: | M D P I AG | ||||||
| ISSN: | 1422-0067 | ||||||
| Official Date: | 6 July 2021 | ||||||
| Dates: |
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| Volume: | 22 | ||||||
| Number: | 14 | ||||||
| Article Number: | 7254 | ||||||
| DOI: | 10.3390/ijms22147254 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||
| Date of first compliant deposit: | 7 July 2021 | ||||||
| Date of first compliant Open Access: | 8 July 2021 | ||||||
| RIOXX Funder/Project Grant: |
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| Is Part Of: | 1 |
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