TTX-Resistant Sodium Channels Functionally Separate Silent From Polymodal C-nociceptors
Pronounced activity-dependent slowing of conduction has been used to characterize mechano-insensitive, “silent” nociceptors and might be due to high expression of NaV1.8 and could, therefore, be characterized by their tetrodotoxin-resistance (TTX-r). Nociceptor-class specific differences in action p...
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2020.00013/full |
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| author | Robin Jonas Vincenzo Prato Stefan G. Lechner Gerbrand Groen Otilia Obreja Fiona Werland Roman Rukwied Andreas Klusch Marlen Petersen Richard W. Carr Martin Schmelz |
| author_facet | Robin Jonas Vincenzo Prato Stefan G. Lechner Gerbrand Groen Otilia Obreja Fiona Werland Roman Rukwied Andreas Klusch Marlen Petersen Richard W. Carr Martin Schmelz |
| author_sort | Robin Jonas |
| collection | DOAJ |
| description | Pronounced activity-dependent slowing of conduction has been used to characterize mechano-insensitive, “silent” nociceptors and might be due to high expression of NaV1.8 and could, therefore, be characterized by their tetrodotoxin-resistance (TTX-r). Nociceptor-class specific differences in action potential characteristics were studied by: (i) in vitro calcium imaging in single porcine nerve growth factor (NGF)-responsive neurites; (ii) in vivo extracellular recordings in functionally identified porcine silent nociceptors; and (iii) in vitro patch-clamp recordings from murine silent nociceptors, genetically defined by nicotinic acetylcholine receptor subunit alpha-3 (CHRNA3) expression. Porcine TTX-r neurites (n = 26) in vitro had more than twice as high calcium transients per action potential as compared to TTX-s neurites (n = 18). In pig skin, silent nociceptors (n = 14) characterized by pronounced activity-dependent slowing of conduction were found to be TTX-r, whereas polymodal nociceptors were TTX-s (n = 12) and had only moderate slowing. Mechano-insensitive cold nociceptors were also TTX-r but showed less activity-dependent slowing than polymodal nociceptors. Action potentials in murine silent nociceptors differed from putative polymodal nociceptors by longer duration and higher peak amplitudes. Longer duration AP in silent murine nociceptors linked to increased sodium load would be compatible with a pronounced activity-dependent slowing in pig silent nociceptors and longer AP durations could be in line with increased calcium transients per action potential observed in vitro in TTX-resistant NGF responsive porcine neurites. Even though there is no direct link between slowing and TTX-resistant channels, the results indicate that axons of silent nociceptors not only differ in their receptive but also in their axonal properties. |
| first_indexed | 2024-12-14T03:39:09Z |
| format | Article |
| id | doaj.art-940d087a68b74902b0e07b9c69eb24d5 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-14T03:39:09Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-940d087a68b74902b0e07b9c69eb24d52022-12-21T23:18:31ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022020-02-011410.3389/fncel.2020.00013507160TTX-Resistant Sodium Channels Functionally Separate Silent From Polymodal C-nociceptorsRobin Jonas0Vincenzo Prato1Stefan G. Lechner2Gerbrand Groen3Otilia Obreja4Fiona Werland5Roman Rukwied6Andreas Klusch7Marlen Petersen8Richard W. Carr9Martin Schmelz10Department of Experimental Pain Research, Medical Faculty Mannheim, University of Heidelberg, Mannheim, GermanyInstitute of Pharmacology, University of Heidelberg, Heidelberg, GermanyInstitute of Pharmacology, University of Heidelberg, Heidelberg, GermanyDepartment of Anesthesiology, Groningen University, Groningen, NetherlandsDepartment of Experimental Pain Research, Medical Faculty Mannheim, University of Heidelberg, Mannheim, GermanyDepartment of Experimental Pain Research, Medical Faculty Mannheim, University of Heidelberg, Mannheim, GermanyDepartment of Experimental Pain Research, Medical Faculty Mannheim, University of Heidelberg, Mannheim, GermanyDepartment of Experimental Pain Research, Medical Faculty Mannheim, University of Heidelberg, Mannheim, GermanyDepartment of Experimental Pain Research, Medical Faculty Mannheim, University of Heidelberg, Mannheim, GermanyDepartment of Experimental Pain Research, Medical Faculty Mannheim, University of Heidelberg, Mannheim, GermanyDepartment of Experimental Pain Research, Medical Faculty Mannheim, University of Heidelberg, Mannheim, GermanyPronounced activity-dependent slowing of conduction has been used to characterize mechano-insensitive, “silent” nociceptors and might be due to high expression of NaV1.8 and could, therefore, be characterized by their tetrodotoxin-resistance (TTX-r). Nociceptor-class specific differences in action potential characteristics were studied by: (i) in vitro calcium imaging in single porcine nerve growth factor (NGF)-responsive neurites; (ii) in vivo extracellular recordings in functionally identified porcine silent nociceptors; and (iii) in vitro patch-clamp recordings from murine silent nociceptors, genetically defined by nicotinic acetylcholine receptor subunit alpha-3 (CHRNA3) expression. Porcine TTX-r neurites (n = 26) in vitro had more than twice as high calcium transients per action potential as compared to TTX-s neurites (n = 18). In pig skin, silent nociceptors (n = 14) characterized by pronounced activity-dependent slowing of conduction were found to be TTX-r, whereas polymodal nociceptors were TTX-s (n = 12) and had only moderate slowing. Mechano-insensitive cold nociceptors were also TTX-r but showed less activity-dependent slowing than polymodal nociceptors. Action potentials in murine silent nociceptors differed from putative polymodal nociceptors by longer duration and higher peak amplitudes. Longer duration AP in silent murine nociceptors linked to increased sodium load would be compatible with a pronounced activity-dependent slowing in pig silent nociceptors and longer AP durations could be in line with increased calcium transients per action potential observed in vitro in TTX-resistant NGF responsive porcine neurites. Even though there is no direct link between slowing and TTX-resistant channels, the results indicate that axons of silent nociceptors not only differ in their receptive but also in their axonal properties.https://www.frontiersin.org/article/10.3389/fncel.2020.00013/fulltetrodotoxinactivity-dependent slowing of conductionaxonal calcium imagingaction potential conductionnociceptor classes |
| spellingShingle | Robin Jonas Vincenzo Prato Stefan G. Lechner Gerbrand Groen Otilia Obreja Fiona Werland Roman Rukwied Andreas Klusch Marlen Petersen Richard W. Carr Martin Schmelz TTX-Resistant Sodium Channels Functionally Separate Silent From Polymodal C-nociceptors Frontiers in Cellular Neuroscience tetrodotoxin activity-dependent slowing of conduction axonal calcium imaging action potential conduction nociceptor classes |
| title | TTX-Resistant Sodium Channels Functionally Separate Silent From Polymodal C-nociceptors |
| title_full | TTX-Resistant Sodium Channels Functionally Separate Silent From Polymodal C-nociceptors |
| title_fullStr | TTX-Resistant Sodium Channels Functionally Separate Silent From Polymodal C-nociceptors |
| title_full_unstemmed | TTX-Resistant Sodium Channels Functionally Separate Silent From Polymodal C-nociceptors |
| title_short | TTX-Resistant Sodium Channels Functionally Separate Silent From Polymodal C-nociceptors |
| title_sort | ttx resistant sodium channels functionally separate silent from polymodal c nociceptors |
| topic | tetrodotoxin activity-dependent slowing of conduction axonal calcium imaging action potential conduction nociceptor classes |
| url | https://www.frontiersin.org/article/10.3389/fncel.2020.00013/full |
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