The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain
Open accessAbstract
Voltage-gated sodium (Nav) channels initiate action potentials in most neurons, including primary afferent nerve fibres of the pain pathway. Local anaesthetics block pain through non-specific actions at all Nav channels, but the discovery of selective modulators would facilitate the analysis of individual subtypes of these channels and their contributions to chemical, mechanical, or thermal pain. Here we identify and characterize spider (Heteroscodra maculata) toxins that selectively activate the Nav1.1 subtype, the role of which in nociception and pain has not been elucidated. We use these probes to show that Nav1.1-expressing fibres are modality-specific nociceptors: their activation elicits robust pain behaviours without neurogenic inflammation and produces profound hypersensitivity to mechanical, but not thermal, stimuli. In the gut, high-threshold mechanosensitive fibres also express Nav1.1 and show enhanced toxin sensitivity in a mouse model of irritable bowel syndrome. Together, these findings establish an unexpected role for Nav1.1 channels in regulating the excitability of sensory nerve fibres that mediate mechanical pain.
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Cites
Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing
Usoskin, D., Furlan, A., Islam, S., Abdo, H., Lönnerberg, P., Lou, D., Hjerling-Leffler, J., Haeggström, J., Kharchenko, O., Kharchenko, P. V., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.3881 · Cited by 2,136
Autistic-like behaviour in Scn1a+/− mice and rescue by enhanced GABA-mediated neurotransmission
Han, S., Tai, C., Westenbroek, R. E., Yu, F. H., Cheah, C. S., Potter, G. B., Rubenstein, J. L., Scheuer, T., de la Iglesia, H. O., & Catterall, W. A. (2012) · Nature · doi:10.1038/nature11356 · Cited by 643
Catterall, W. A., Kalume, F., & Oakley, J. C. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.187484 · Cited by 428 · cited 1×
“Mutations affecting Na v 1.1 are associated with central nervous system (CNS) disorders such as epilepsy 12,13 , autism 14 , and Alzheimer’s 15 , and these clinically dominant phenotypes may have masked roles for this subtype in peripheral neurons.”
InfluentialCheah, C. S., Yu, F. H., Westenbroek, R. E., Kalume, F. K., Oakley, J. C., Potter, G. B., Rubenstein, J. L., & Catterall, W. A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211591109 · Cited by 336
Castro, J., Harrington, A. M., Hughes, P. A., Martin, C. M., Ge, P., Shea, C. M., Jin, H., Jacobson, S., Hannig, G., Mann, E., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.08.017 · Cited by 295
Self-citationMcCormack, K., Santos, S., Chapman, M. L., Krafte, D. S., Marron, B. E., West, C. W., Krambis, M. J., Antonio, B. M., Zellmer, S. G., Printzenhoff, D., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220844110 · Cited by 244
Cited by
The Role of Voltage-Gated Sodium Channels in Pain Signaling
Bennett, D. L., Clark, A. J., Huang, J., Waxman, S. G., & Dib-Hajj, S. D. (2019) · Physiological Reviews · doi:10.1152/physrev.00052.2017 · Cited by 730
Ion Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies
Oyrer, J., Maljevic, S., Scheffer, I. E., Berkovic, S. F., Petrou, S., & Reid, C. A. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014456 · Cited by 315
Favero, M., Sotuyo, N. P., Lopez, E., Kearney, J. A., & Goldberg, E. M. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.0193-18.2018 · Cited by 163
Goff, K. M., & Goldberg, E. M. (2019) · eLife · doi:10.7554/elife.46846 · Cited by 93
Metadata
- Authors
- Osteen, J. D., Herzig, V., Gilchrist, J., Emrick, J. J., Zhang, C., Wang, X., Castro, J., Garcia-Caraballo, S., Grundy, L., Rychkov, G. Y., Weyer, A. D., Dekan, Z., Undheim, E. A. B., Alewood, P., Stucky, C. L., Brierley, S. M., Basbaum, A. I., Bosmans, F., King, G. F., & Julius, D.
- Venue
- Nature
- Published
- 2016-06-06
- Volume
- 534
- Issue
- 7608
- Pages
- 494-499
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2409924309
- Cited by
- 293
- References
- 6
- FWCI
- 27.83
- Type
- journal article
- Language
- en
- Open access
- green
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