The mammalian sodium channel BNC1 is required for normal touch sensation

A Corrigendum to this article was published on 18 July 2002

Abstract

Of the vertebrate senses, touch is the least understood at the molecular level. The ion channels that form the core of the mechanosensory complex and confer touch sensitivity remain unknown1,2,3. However, the similarity of the brain sodium channel 1 (BNC1)4,5,6 to nematode proteins involved in mechanotransduction indicated that it might be a part of such a mechanosensor7,8. Here we show that disrupting the mouse BNC1 gene markedly reduces the sensitivity of a specific component of mechanosensation: low-threshold rapidly adapting mechanoreceptors. In rodent hairy skin these mechanoreceptors are excited by hair movement2. Consistent with this function, we found BNC1 in the lanceolate nerve endings that lie adjacent to and surround the hair follicle9. Although BNC1 has been proposed to have a role in pH sensing10,11, the acid-evoked current in cultured sensory neurons and the response of acid-stimulated nociceptors were normal in BNC1 null mice. These data identify the BNC1 channel as essential for the normal detection of light touch and indicate that BNC1 may be a central component of a mechanosensory complex.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Disruption of BNC1 locus.
Figure 2: Mechanosensitivity of wild-type and BNC1 null mice.
Figure 3: Response of sensory neurons to current injection, acidic pH and heat.
Figure 4: Immunostaining of BNC1 around guard hair follicles.

References

  1. 1

    Johnson, K. O. & Hsiao, S. S. Neural mechanisms of tactual form and texture perception. Annu. Rev. Neurosci. 15, 227–250 (1992).

    CAS  Article  Google Scholar 

  2. 2

    Perl, E. R. in Sensory Neuron: Diversity, Development, and Plasticity (ed. Scott, S. A.) 3–23 (Oxford Univ. Press, Oxford, 1992).

    Google Scholar 

  3. 3

    Caterina, M. J. & Julius, D. Sense and specificity: a molecular identity for nociceptors. Curr. Opin. Neurobiol. 9, 525–530 (1999).

    CAS  Article  Google Scholar 

  4. 4

    Price, M. P., Snyder, P. M. & Welsh, M. J. Cloning and expression of a novel human brain Na+ channel. J. Biol. Chem. 271, 7879 –7882 (1996).

    CAS  Article  Google Scholar 

  5. 5

    Waldmann, R., Champigny, G., Voilley, N., Lauritzen, I. & Lazdunski, M. The mammalian degenerin MDEG, an amiloride-sensitive cation channel activated by mutations causing neurodegeneration in Caenorhabditis elegans. J. Biol. Chem. 271 , 10433–10436 (1996).

    CAS  Article  Google Scholar 

  6. 6

    García-Añoveros, J., Derfler, B., Neville-Golden, J., Hyman, B. T. & Corey, D. P. BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels. Proc. Natl Acad. Sci. USA 94, 1459–1464 (1997).

    ADS  Article  Google Scholar 

  7. 7

    Tavernarakis, N. & Driscoll, M. Molecular modeling of mechanotransduction in the nematode Caenorhabditis elegans. Annu. Rev. Physiol. 59, 659–689 (1997).

    CAS  Article  Google Scholar 

  8. 8

    García-Añoveros, J. & Corey, D. P. The molecules of mechanosensation. Annu. Rev. Neurosci. 20, 567–594 (1997).

    Article  Google Scholar 

  9. 9

    Halata, Z. Sensory innervation of the hairy skin (light- and electronmicroscopic study). J. Invest. Derm. 101, 75s– 81s (1993).

    CAS  Article  Google Scholar 

  10. 10

    Waldmann, R. & Lazdunski, M. H+-gated cation channels: neuronal acid sensors in the NaC/DEG family of ion channels. Curr. Opin. Neurobiol. 8, 418–424 (1998).

    CAS  Article  Google Scholar 

  11. 11

    Bassilana, F. et al. The acid-sensitive ionic channel subunit ASIC and the mammalian degenerin MDEG form a heteromultimeric H+-gated Na+ channel with novel properties. J. Biol. Chem. 272, 28819–28822 (1997).

    CAS  Article  Google Scholar 

  12. 12

    Mano, I. & Driscoll, M. DEG/ENaC channels: a touchy superfamily that watches its salt. Bioessays 21, 568 –578 (1999).

    CAS  Article  Google Scholar 

  13. 13

    Driscoll, M. & Chalfie, M. The mec-4 gene is a member of a family of Caenorhabditis elegans genes that can mutate to induce neuronal degeneration. Nature 349, 588– 593 (1991).

    ADS  CAS  Article  Google Scholar 

  14. 14

    Huang, M. & Chalfie, M. Gene interactions affecting mechanosensory transduction in Caenorhabditis elegans. Nature 367, 467–470 (1994).

    ADS  CAS  Article  Google Scholar 

  15. 15

    Lingueglia, E. et al. A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells. J. Biol. Chem. 272, 29778–29783 (1997).

    CAS  Article  Google Scholar 

  16. 16

    Koltzenburg, M., Stucky, C. L. & Lewin, G. R. Receptive properties of mouse sensory neurons innervating hairy skin. J. Neurophysiol. 78, 1841– 1850 (1997).

    CAS  Article  Google Scholar 

  17. 17

    Carroll, P., Lewin, G. R., Koltzenburg, M., Toyka, K. V. & Thoenen, H. A role for BDNF in mechanosensation. Nature Neurosci. 1, 42– 46 (1998).

    CAS  Article  Google Scholar 

  18. 18

    French, A. S. Mechanotransduction. Annu. Rev. Physiol. 54, 135–152 (1992).

    CAS  Article  Google Scholar 

  19. 19

    Koerber, H. R., Druzinsky, R. E. & Mendell, L. M. Properties of somata of spinal dorsal root ganglion cells differ according to peripheral receptor innervated. J. Neurophysiol. 60, 1584–1596 ( 1988).

    CAS  Article  Google Scholar 

  20. 20

    Krishtal, O. A. & Pidoplichko, V. I. A receptor for protons in the membrane of sensory neurons may participate in nociception. Neuroscience 6, 2599–2601 (1981).

    CAS  Article  Google Scholar 

  21. 21

    Bevan, S. & Yeats, J. protons activate a cation conductance in a sub-population of rat dorsal root ganglion neurons. J. Physiol. (Lond.) 433, 145–161 ( 1991).

    CAS  Article  Google Scholar 

  22. 22

    Steen, K. H., Reeh, P. W., Anton, F. & Handwerker, H. O. Protons selectively induce lasting excitation and sensitization to mechanical stimulation of nociceptors in rat skin, in vitro. J. Neurosci. 12, 86–95 (1992).

    CAS  Article  Google Scholar 

  23. 23

    Walker, R. G., Willingham, A. T. & Zuker, C. S. A Drosophila mechanosensory transduction channel. Science 287, 2229–2234 (2000).

    ADS  CAS  Article  Google Scholar 

  24. 24

    Rusch, A. & Hummler, E. Mechano-electrical transduction in mice lacking the alpha-subunit of the epithelial sodium channel. Hear. Res. 131, 170–176 (1999).

    CAS  Article  Google Scholar 

  25. 25

    Fricke, B. et al. Epithelial Na+ channels and stomatin are expressed in rat trigeminal mechanosensory neurons. Cell Tissue Res. 299, 327–334 (2000).

    CAS  PubMed  Google Scholar 

  26. 26

    Drummond, H. A., Abboud, F. M. & Welsh, M. J. Localization of β and γ subunits of ENaC in sensory nerve endings in the rat foot pad. Brain Res. (in the press).

  27. 27

    McDonald, F. M. et al. Disruption of the β subunit of the epithelial Na+ channel in mice: hyperkalemia and neonatal death associated with a pseudohypoaldosteronism phenotype. Proc. Natl Acad. Sci. USA 96, 1727–1731 ( 1999).

    ADS  CAS  Article  Google Scholar 

  28. 28

    Mannsfeldt, A. G., Carroll, P., Stucky, C. L. & Lewin, G. R. Stomatin, a MEC-2 like protein, is expressed by mammalian sensory neurons. Mol. Cell. Neurosci. 13, 391– 404 (1999).

    CAS  Article  Google Scholar 

  29. 29

    Benson, C. J., Eckert, S. P. & McCleskey, E. W. Acid-evoked currents in cardiac sensory neurons: a possible mediator of myocardial ischemic sensation. Circ. Res. 84, 921–928 ( 1999).

    CAS  Article  Google Scholar 

  30. 30

    Stucky, C. L. & Lewin, G. R. Isolectin B4-positive and -negative nociceptors are functionally distinct. J. Neurosci. 19, 6497–6505 ( 1999).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We thank D. Melssen, E. Tarr, T. Moninger, R. Hrstka, T. Nesselhauf, P. Weber, A. Kanehl and T. Mayhew for assistance. We also thank the University of Iowa DNA Core Facility and the Central Microscopy Facility for assistance. This work was supported by the HHMI (M.J.W.) and a DFG grant (G.R.L.). P.A.H. was supported by a Marie Curie fellowship from the European Union. M.J.W. is an Investigator of the HHMI.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Michael J. Welsh.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Price, M., Lewin, G., McIlwrath, S. et al. The mammalian sodium channel BNC1 is required for normal touch sensation . Nature 407, 1007–1011 (2000). https://doi.org/10.1038/35039512

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing