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A single mechanism driving both inactivation and adaptation in rapidly adapting currents of DRG neurons?

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Abstract

Rapidly adapting (RA) currents expressed in dorsal root ganglia somatosensory neurons reduce their amplitude in response to prolonged and/or repeated mechanical stimulation. Both inactivation of mechanotransducer channels and adaptation of the force acting on the channels have been suggested to independently decrease RA currents. However, these two mechanisms have similar kinetics and dependence on calcium and voltage. These experimental findings suggest that a single mechanism might underlie both. We constructed a simple Hodgkin–Huxley-type model with a single gating variable driving both inactivation and adaptation to test this hypothesis. Predictions of the model successfully describe key features of mechanical activation as well as inactivation, adaptation, and recovery. The model thus supports the possibility of a single mechanism driving inactivation and adaptation in RA currents. On its own, the model can be integrated into higher-order models of touch receptors because of its accurate simulation of RA currents.

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References

  1. Drew LJ, Wood JN, Cesare P (2002) Distinct mechanosensitive properties of capsaicin-sensitive and -insensitive sensory neurons. J. Neurosci 22:RC228:(1–5)

  2. Hu J, Lewin GR (2006) Mechanosensitive currents in the neurites of cultured mouse sensory neurones. J Physiol 577(Pt 3):815–828. doi:10.1113/jphysiol.2006.117648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hao J, Delmas P (2010) Multiple desensitization mechanisms of mechanotransducer channels shape firing of mechanosensory neurons. J Neurosci 30(40):13384–13395. doi:10.1523/JNEUROSCI.2926-10.2010

    Article  CAS  PubMed  Google Scholar 

  4. Rugiero F, Drew LJ, Wood JN (2010) Kinetic properties of mechanically activated currents in spinal sensory neurons. J Physiol 588(Pt 2):301–314. doi:10.1113/jphysiol.2009.182360

    Article  CAS  PubMed  Google Scholar 

  5. Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE, Patapoutian A (2010) Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330(6000):55–60. doi:10.1126/science.1193270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ranade SS, Woo SH, Dubin AE, Moshourab RA, Wetzel C, Petrus M, Mathur J, Bégay V, Coste B, Mainquist J, Wilson AJ, Francisco AG, Reddy K, Qiu Z, Wood JN, Lewin GR, Patapoutian A (2014) Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature 516(7526):121–125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hao J, Bonnet C, Amsalem M, Ruel J, Delmas P (2015) Transduction and encoding sensory information by skin mechanoreceptors. Eur J Physiol 467(1):109–119

    Article  CAS  Google Scholar 

  8. Drew LJ, Rohrer DK, Price MP, Blaver KE, Cockayne DA, Cesare P, Wood JN (2004) Acid-sensing ion channels ASIC2 and ASIC3 do not contribute to mechanically activated currents in mammalian sensory neurones. J Physiol 556(Pt 3):691–710. doi:10.1113/jphysiol.2003.058693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Eatock RA, Corey DP, Hudspeth AJ (1987) Adaptation of mechanoelectrical transduction in hair cells of the bullfrog’s sacculus. J Neurosci 7(9):2821–2836

    CAS  PubMed  Google Scholar 

  10. Eatock RA (2000) Adaptation in hair cells. Annu Rev Neurosci 23:285–314. doi:10.1146/annurev.neuro.23.1.285

    Article  CAS  PubMed  Google Scholar 

  11. Gillespie PG, Müller U (2009) Mechanotransduction by Hair Cells. Cell 139(1):33–44. doi:10.1016/j.cell.2009.09.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Armstrong CM (1981) Sodium channels and gating currents. Physiol Rev 61(3):644–683

    CAS  PubMed  Google Scholar 

  13. Kellenberger S, Scheuer T, Catterall WA (1996) Movement of the Na+ channel inactivation gate during inactivation. J Biol Chem 271(48):30971–30979

    Article  CAS  PubMed  Google Scholar 

  14. Shin KS, Maertens C, Proenza C, Rothberg BS, Yellen G (2004) Inactivation in HCN channels results from reclosure of the activation gate: desensitization to voltage. Neuron 41(5):737–744

    Article  CAS  PubMed  Google Scholar 

  15. Akitake B, Anishkin A, Sukharev S (2005) The dashpot mechanism of stretch-dependent gating in MscS. J Gen Physiol 125:143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Belyy V, Anishkin A, Kamaraju K, Liu N, Sukharev S (2010) The tension-transmitting’clutch’ in the mechanosensitive channel MscS. Nature Structural and Molecular Biology 17(4):451

  17. Howard J, Roberts WM, Hudspeth AJ (1988) Mechanoelectrical transduction by hair cells. Annu Rev Biophys Biophys Chem 17:99–124. doi:10.1146/annurev.bb.17.060188.000531

    Article  CAS  PubMed  Google Scholar 

  18. Hao J, Padilla F, Dandonneau M, Lavebratt C, Lesage F, Noël J, Delmas P (2013) Kv1. 1 channels act as mechanical brake in the senses of touch and pain. Neuron 77(5):899–914. doi:10.1016/j.neuron.2012.12.035

    Article  CAS  PubMed  Google Scholar 

  19. Coste B, Xiao B, Santos JS, Syeda R, Grandl J, Spencer KS, Kim SE, Schmidt M, Mathur J, Dubin AE, Montal M, Patapoutian A (2012) Piezo proteins are pore-forming subunits of mechanically activated channels. Nature 483(7388):176–181. doi:10.1038/nature10812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Katta S, Krieg M, Goodman MB (2015) Feeling force: physical and physiological principles enabling sensory mechanotransduction. Annu Rev Cell Dev Biol 31:347–371

    Article  CAS  PubMed  Google Scholar 

  21. Gottlieb PA, Bae C, Sachs F (2012) Gating the mechanical channel Piezo1: a comparison between whole-cell and patch recording. Channels (Austin) 6(4):282–289. doi:10.4161/chan.21064

  22. Coste B, Houge G, Murray MF, Stitzield N, Bandelle M, Giovanni MA, Philippakis A, Hoischen A, Riemer G, Steen U, Steen VM, Mathur J, Cox J, Lebo M, Rehm H, Weiss ST, Wood JN, Maas RL, Sunyaev SR, Patapoutian A (2013) Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis. Proc Natl Acad Sci USA 110:4667–4672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ranade SS, Syeda R, Patapoutian A (2015) Mechanically activated ion channels. Neuron 87:1162–1179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hu J, Chiang LY, Koch M, Lewin GR (2010) Evidence for a protein tether involved in somatic touch. EMBO J 29(4):855–867. doi:10.1038/emboj.2009.398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kung C (2005) A possible unifying principle for mechanosensation. Nature 436(7051):647–654. doi:10.1038/nature03896

    Article  CAS  PubMed  Google Scholar 

  26. Hardie RC, Franze K (2012) Photomechanical responses in Drosophila photoreceptors. Science 338(6104):260–263. doi:10.1126/science.1222376

    Article  CAS  PubMed  Google Scholar 

  27. Sukharev S, Sachs F (2012) Molecular force transduction by ion channels–diversity and unifying principles. J Cell Sci 125:3075–3083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Vodlak T, Vidrih Z, Pirih P, Škorjanc A, Prešern J, Rodič T (2014) Functional microanatomical model of Meissner corpuscl. In: Haptics: Neuroscience, Devices, Modeling, and Applications (Springer), pp. 377–384

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Acknowledgments

We are grateful to Drs Patrick Delmas and Jizhé Hao for sending us some of the experimental data and to Eric James McDermott for proofreading.

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Authors and Affiliations

  1. Department of Apiculture, Agricultural Institute of Slovenia, Hacquetova ul. 17, 1000, Ljubljana, Slovenia

    Janez Prešern

  2. Department of Biology, Biotechnical Faculty, University of Ljubljana, Večna pot 111, 1000, Ljubljana, Slovenia

    Aleš Škorjanc

  3. Faculty of Natural sciences and Engineering, University of Ljubljana, Aškerčeva cesta 12, 1000, Ljubljana, Slovenia

    Tomaž Rodič

  4. Institute for Neurobiology, University of Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany

    Jan Benda

Authors
  1. Janez Prešern
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  2. Aleš Škorjanc
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  3. Tomaž Rodič
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  4. Jan Benda
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Corresponding author

Correspondence to Jan Benda.

Additional information

TR was supported by EU FP7 NanoBioTouch. JB was supported by BMBF Bernstein Award Computational Neuroscience 01GQ0802. JP received support from the Slovenian Research Agency, project ARRS-Z3-4061, and AŠ received support from the Slovenian Research Agency, project ARRS-Z1-4288.

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Prešern, J., Škorjanc, A., Rodič, T. et al. A single mechanism driving both inactivation and adaptation in rapidly adapting currents of DRG neurons?. Biol Cybern 110, 393–401 (2016). https://doi.org/10.1007/s00422-016-0693-7

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  • DOI: https://doi.org/10.1007/s00422-016-0693-7

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