Change search
ReferencesLink to record
Permanent link

Direct link
C-Fiber Recovery Cycle Supernormality Depends on Ion Concentration and Ion Channel Permeability
KTH, School of Computer Science and Communication (CSC), Computational Biology, CB. Stockholm Brain Institute, Sweden.
KTH, School of Computer Science and Communication (CSC), Computational Biology, CB. Stockholm Brain Institute, Sweden.
Show others and affiliations
2015 (English)In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 108, no 5, 1057-1071 p.Article in journal (Refereed) Published
Abstract [en]

Following each action potential, C-fiber nociceptors undergo cyclical changes in excitability, including a period of superexcitability, before recovering their basal excitability state. The increase in superexcitability during this recovery cycle depends upon their immediate firing history of the axon, but also determines the instantaneous firing frequency that encodes pain intensity. To explore the mechanistic underpinnings of the recovery cycle phenomenon a biophysical model of a C-fiber has been developed. The model represents the spatial extent of the axon including its passive properties as well as ion channels and the Na/K-ATPase ion pump. Ionic concentrations were represented inside and outside the membrane. The model was able to replicate the typical transitions in excitability from subnormal to supernormal observed empirically following a conducted action potential. In the model, supernormality depended on the degree of conduction slowing which in turn depends upon the frequency of stimulation, in accordance with experimental findings. In particular, we show that activity-dependent conduction slowing is produced by the accumulation of intraaxonal sodium. We further show that the supernormal phase results from a reduced potassium current K-dr as a result of accumulation of periaxonal potassium in concert with a reduced influx of sodium through Na(v)1.7 relative to Na(v)1.8 current. This theoretical prediction was supported by data from an in vitro preparation of small rat dorsal root ganglion somata showing a reduction in the magnitude of tetrodotoxin-sensitive relative to tetrodotoxin - resistant whole cell current. Furthermore, our studies provide support for the role of depolarization in supernormality, as previously suggested, but we suggest that the basic mechanism depends on changes in ionic concentrations inside and outside the axon. The understanding of the mechanisms underlying repetitive discharges in recovery cycles may provide insight into mechanisms of spontaneous activity, which recently has been shown to correlate to a perceived level of pain.

Place, publisher, year, edition, pages
2015. Vol. 108, no 5, 1057-1071 p.
Keyword [en]
Innervating Human Skin, Repetitive Stimulation, Electrical-Stimulation, Diabetic-Neuropathy, Nerve Excitability, Spontaneous Pain, Sensory Neurons, Nociceptors, Conduction, Inactivation
National Category
Bioinformatics (Computational Biology)
URN: urn:nbn:se:kth:diva-165975DOI: 10.1016/j.bpj.2014.12.034ISI: 000350969000008PubMedID: 25762318ScopusID: 2-s2.0-84924787587OAI: diva2:809226
Swedish Research Council, VR 621-2007-4223

QC 20150504

Available from: 2015-04-30 Created: 2015-04-30 Last updated: 2015-05-04Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Tigerholm, JennyPetersson, Marcus E.Fransén, Erik
By organisation
Computational Biology, CB
In the same journal
Biophysical Journal
Bioinformatics (Computational Biology)

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 75 hits
ReferencesLink to record
Permanent link

Direct link