Pflügers Archiv - European Journal of Physiology

, Volume 467, Issue 1, pp 101–108 | Cite as

Mechanotransduction in epidermal Merkel cells

  • Masashi Nakatani
  • Srdjan Maksimovic
  • Yoshichika Baba
  • Ellen A. Lumpkin
Invited Review


The cellular and molecular basis of vertebrate touch reception remains least understood among the traditional five senses. Somatosensory afferents that innervate the skin encode distinct tactile qualities, such as flutter, slip, and pressure. Gentle touch is thought to be transduced by somatosensory afferents whose tactile end organs selectively filter mechanical stimuli. These tactile end organs comprise afferent terminals in association with non-neuronal cell types such as Merkel cells, keratinocytes, and Schwann cells. An open question is whether these non-neuronal cells serve primarily as passive mechanical filters or whether they actively participate in mechanosensory transduction. This question has been most extensively studied in Merkel cells, which are epidermal cells that complex with sensory afferents in regions of high tactile acuity such as fingertips, whisker follicles, and touch domes. Merkel cell-neurite complexes mediate slowly adapting type I (SAI) responses, which encode sustained pressure and represent object features with high fidelity. How Merkel cells contribute to unique SAI firing patterns has been debated for decades; however, three recent studies in rodent models provide some direct answers. First, whole-cell recordings demonstrate that Merkel cells are touch-sensitive cells with fast, mechanically activated currents that require Piezo2. Second, optogenetics and intact recordings show that Merkel cells mediate sustained SAI firing. Finally, loss-of-function studies in transgenic mouse models reveal that SAI afferents are also touch sensitive. Together, these studies identify molecular mechanisms of mechanotransduction in Merkel cells, reveal unexpected functions for these cells in touch, and support a revised, two-receptor site model of mechanosensory transduction.


Touch Piezo2 Mechanosensitive channels Mechanosensory cells Tactile 



We thank Ms. Blair Jenkins for assistance with figures and members of the Lumpkin lab for discussions. The authors are supported by National Institutes of Health grants R01AR051219 (to EAL) and R01NS073119 (to EAL and Gregory J. Gerling), and fellowships to MN (Japan Society for the Promotion of Science Research Fellowships for Young Scientists 24-7585) and SM (F32NS080544).


  1. 1.
    Bechstedt S, Howard J (2008) Hearing mechanics: a fly in your ear. Curr Biol : CB 18(18):R869–R870. doi: 10.1016/j.cub.2008.07.069 PubMedCrossRefGoogle Scholar
  2. 2.
    Ben-Arie N, Hassan BA, Bermingham NA, Malicki DM, Armstrong D, Matzuk M, Bellen HJ, Zoghbi HY (2000) Functional conservation of atonal and Math1 in the CNS and PNS. Development 127(5):1039–1048PubMedGoogle Scholar
  3. 3.
    Boulais N, Pennec JP, Lebonvallet N, Pereira U, Rougier N, Dorange G, Chesne C, Misery L (2009) Rat Merkel cells are mechanoreceptors and osmoreceptors. PLoS ONE 4(11):e7759. doi: 10.1371/journal.pone.0007759 PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Boulais N, Pereira U, Lebonvallet N, Gobin E, Dorange G, Rougier N, Chesne C, Misery L (2009) Merkel cells as putative regulatory cells in skin disorders: an in vitro study. PLoS ONE 4(8):e6528. doi: 10.1371/journal.pone.0006528 PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8(9):1263–1268. doi: 10.1038/nn1525 PubMedCrossRefGoogle Scholar
  6. 6.
    Cha M, Ling J, Xu GY, Gu JG (2011) Shear mechanical force induces an increase of intracellular Ca2+ in cultured Merkel cells prepared from rat vibrissal hair follicles. J Neurophysiol 106(1):460–469. doi: 10.1152/jn.00274.2011 PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Chalfie M (2009) Neurosensory mechanotransduction. Nat Rev Mol Cell Biol 10(1):44–52. doi: 10.1038/nrm2595 PubMedCrossRefGoogle Scholar
  8. 8.
    Chan E, Yung WH, Baumann KI (1996) Cytoplasmic Ca2+ concentrations in intact Merkel cells of an isolated, functioning rat sinus hair preparation. Exp Brain Res 108(3):357–366PubMedCrossRefGoogle Scholar
  9. 9.
    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 PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    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 PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Delmas P, Hao J, Rodat-Despoix L (2011) Molecular mechanisms of mechanotransduction in mammalian sensory neurons. Nat Rev Neurosci 12(3):139–153. doi: 10.1038/nrn2993 PubMedCrossRefGoogle Scholar
  12. 12.
    Diamond J, Mills LR, Mearow KM (1988) Evidence that the Merkel cell is not the transducer in the mechanosensory Merkel cell-neurite complex. Prog Brain Res 74:51–56PubMedCrossRefGoogle Scholar
  13. 13.
    Fagan BM, Cahusac PM (2001) Evidence for glutamate receptor mediated transmission at mechanoreceptors in the skin. Neuroreport 12(2):341–347PubMedCrossRefGoogle Scholar
  14. 14.
    Gottschaldt KM, Vahle-Hinz C (1981) Merkel cell receptors: structure and transducer function. Science 214(4517):183–186PubMedCrossRefGoogle Scholar
  15. 15.
    Haeberle H, Bryan LA, Vadakkan TJ, Dickinson ME, Lumpkin EA (2008) Swelling-activated Ca2+ channels trigger Ca2+ signals in Merkel cells. PLoS ONE 3(3):e1750. doi: 10.1371/journal.pone.0001750 PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Haeberle H, Fujiwara M, Chuang J, Medina MM, Panditrao MV, Bechstedt S, Howard J, Lumpkin EA (2004) Molecular profiling reveals synaptic release machinery in Merkel cells. Proc Natl Acad Sci U S A 101(40):14503–14508. doi: 10.1073/pnas.0406308101 PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Haeberle H, Lumpkin EA (2008) Merkel cells in somatosensation. Chemosens Percept 1(2):110–118. doi: 10.1007/s12078-008-9012-6 PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Halata Z, Grim M, Bauman KI (2003) Friedrich Sigmund Merkel and his “Merkel cell”, morphology, development, and physiology: review and new results. Anat Rec A: Discov Mol Cell Evol Biol 271(1):225–239. doi: 10.1002/ar.a.10029 CrossRefGoogle Scholar
  19. 19.
    Han X, Chow BY, Zhou H, Klapoetke NC, Chuong A, Rajimehr R, Yang A, Baratta MV, Winkle J, Desimone R, Boyden ES (2011) A high-light sensitivity optical neural silencer: development and application to optogenetic control of non-human primate cortex. Front Syst Neurosci 5:18. doi: 10.3389/fnsys.2011.00018 PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Hao J, Delmas P (2010) Multiple desensitization mechanisms of mechanotransducer channels shape firing of mechanosensory neurons. J Neurosci : Off J Soc Neurosci 30(40):13384–13395. doi: 10.1523/JNEUROSCI.2926-10.2010 CrossRefGoogle Scholar
  21. 21.
    Hitchcock IS, Genever PG, Cahusac PM (2004) Essential components for a glutamatergic synapse between Merkel cell and nerve terminal in rats. Neurosci Lett 362(3):196–199. doi: 10.1016/j.neulet.2004.02.071 PubMedCrossRefGoogle Scholar
  22. 22.
    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 PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Iggo A, Findlater G. Sensory receptor mechanisms. edited by W. Hamann 8:. A. Iggo© 1984 World Scientific Publ. Co., Singapore. In: Proceedings of the International Symposium on Sensory Receptor Mechanisms, 1984. p 117Google Scholar
  24. 24.
    Iggo A, Muir AR (1969) The structure and function of a slowly adapting touch corpuscle in hairy skin. J Physiol 200(3):763–796PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Ikeda I, Yamashita Y, Ono T, Ogawa H (1994) Selective phototoxic destruction of rat Merkel cells abolishes responses of slowly adapting type I mechanoreceptor units. J Physiol 479(Pt 2):247–256PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Ikeda R, Cha M, Ling J, Jia Z, Coyle D, Gu JG (2014) Merkel cells transduce and encode tactile stimuli to drive abeta-afferent impulses. Cell 157(3):664–675. doi: 10.1016/j.cell.2014.02.026 PubMedCrossRefGoogle Scholar
  27. 27.
    Johnson KO (2001) The roles and functions of cutaneous mechanoreceptors. Curr Opin Neurobiol 11(4):455–461. doi: 10.1016/S0959-4388(00)00234-8 PubMedCrossRefGoogle Scholar
  28. 28.
    Johnson KO, Lamb GD (1981) Neural mechanisms of spatial tactile discrimination: neural patterns evoked by braille-like dot patterns in the monkey. J Physiol 310:117–144PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Kinkelin I, Stucky CL, Koltzenburg M (1999) Postnatal loss of Merkel cells, but not of slowly adapting mechanoreceptors in mice lacking the neurotrophin receptor p75. Eur J Neurosci 11(11):3963–3969PubMedCrossRefGoogle Scholar
  30. 30.
    Kwan KY, Glazer JM, Corey DP, Rice FL, Stucky CL (2009) TRPA1 modulates mechanotransduction in cutaneous sensory neurons. J Neurosci : Off J Soc Neurosci 29(15):4808–4819. doi: 10.1523/JNEUROSCI.5380-08.2009 CrossRefGoogle Scholar
  31. 31.
    Lesniak DR, Marshall KL, Wellnitz SA, Jenkins BA, Baba Y, Rasband MN, Gerling GJ, Lumpkin EA (2014) Computation identifies structural features that govern neuronal firing properties in slowly adapting touch receptors. eLife 3:e01488. doi: 10.7554/eLife.01488 PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Lumpkin EA, Collisson T, Parab P, Omer-Abdalla A, Haeberle H, Chen P, Doetzlhofer A, White P, Groves A, Segil N, Johnson JE (2003) Math1-driven GFP expression in the developing nervous system of transgenic mice. Gene Expr Pattern : GEP 3(4):389–395PubMedCrossRefGoogle Scholar
  33. 33.
    Lumpkin EA, Hudspeth AJ (1995) Detection of Ca2+ entry through mechanosensitive channels localizes the site of mechanoelectrical transduction in hair cells. Proc Natl Acad Sci U S A 92(22):10297–10301PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Ma Q (2014) Merkel cells are a touchy subject. Cell 157(3):531–533. doi: 10.1016/j.cell.2014.04.010 PubMedCrossRefGoogle Scholar
  35. 35.
    Maksimovic S, Baba Y, Lumpkin EA (2013) Neurotransmitters and synaptic components in the Merkel cell-neurite complex, a gentle-touch receptor. Ann N Y Acad Sci 1279:13–21. doi: 10.1111/nyas.12057 PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Maksimovic S, Nakatani M, Baba Y, Nelson AM, Marshall KL, Wellnitz SA, Firozi P, Woo SH, Ranade S, Patapoutian A, Lumpkin EA (2014) Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors. Nature 509:617–621. doi: 10.1038/nature13250 PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Maricich SM, Morrison KM, Mathes EL, Brewer BM (2012) Rodents rely on Merkel cells for texture discrimination tasks. J Neurosci : Off JSoc Neurosci 32(10):3296–3300. doi: 10.1523/JNEUROSCI.5307-11.2012 CrossRefGoogle Scholar
  38. 38.
    Maricich SM, Wellnitz SA, Nelson AM, Lesniak DR, Gerling GJ, Lumpkin EA, Zoghbi HY (2009) Merkel cells are essential for light-touch responses. Science 324(5934):1580–1582. doi: 10.1126/science.1172890 PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Merkel F (1875) Tastzellen und Tastkörperchen bei den Hausthieren und beim Menschen. Arch Mikrosk Anat 11(1):636–652. doi: 10.1007/BF02933819 CrossRefGoogle Scholar
  40. 40.
    Mills LR, Diamond J (1995) Merkel cells are not the mechanosensory transducers in the touch dome of the rat. J Neurocytol 24(2):117–134PubMedCrossRefGoogle Scholar
  41. 41.
    Morrison KM, Miesegaes GR, Lumpkin EA, Maricich SM (2009) Mammalian Merkel cells are descended from the epidermal lineage. Dev Biol 336(1):76–83. doi: 10.1016/j.ydbio.2009.09.032 PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Nilius B, Biro T, Owsianik G (2014) TRPV3: time to decipher a poorly understood family member! J Physiol 592(Pt 2):295–304. doi: 10.1113/jphysiol.2013.255968 PubMedCrossRefGoogle Scholar
  43. 43.
    Nunzi MG, Pisarek A, Mugnaini E (2004) Merkel cells, corpuscular nerve endings and free nerve endings in the mouse palatine mucosa express three subtypes of vesicular glutamate transporters. J Neurocytol 33(3):359–376. doi: 10.1023/B:NEUR.0000044196.45602.92 PubMedCrossRefGoogle Scholar
  44. 44.
    Nurse C, Cooper E (1988) Electrophysiological studies on Merkel cells isolated from rat vibrissal mechanoreceptors. In: Hník P, Soukup T, Vejsada R, Zelená J (eds) Mechanoreceptors. Springer, New York, pp 189–194. doi: 10.1007/978-1-4899-0812-4_35 CrossRefGoogle Scholar
  45. 45.
    Pacitti EG, Findlater GS (1988) Calcium channel blockers and Merkel cells. Prog Brain Res 74:37–42PubMedCrossRefGoogle Scholar
  46. 46.
    Pawson L, Prestia LT, Mahoney GK, Guclu B, Cox PJ, Pack AK (2009) GABAergic/glutamatergic-glial/neuronal interaction contributes to rapid adaptation in pacinian corpuscles. J Neurosci : Off J Soc Neurosci 29(9):2695–2705. doi: 10.1523/JNEUROSCI.5974-08.2009 CrossRefGoogle Scholar
  47. 47.
    Phillips JR, Johnson KO (1985) Neural mechanisms of scanned and stationary touch. J Acoust Soc Am 77(1):220–224PubMedCrossRefGoogle Scholar
  48. 48.
    Piskorowski R, Haeberle H, Panditrao MV, Lumpkin EA (2008) Voltage-activated ion channels and Ca2+-induced Ca2+ release shape Ca2+ signaling in Merkel cells. Pflugers Archiv: Eur J Physiol 457(1):197–209. doi: 10.1007/s00424-008-0496-3 CrossRefGoogle Scholar
  49. 49.
    Poole K, Herget R, Lapatsina L, Ngo HD, Lewin GR (2014) Tuning Piezo ion channels to detect molecular-scale movements relevant for fine touch. Nat Commun 5:3520. doi: 10.1038/ncomms4520 PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Press D, Mutlu S, Guclu B (2010) Evidence of fast serotonin transmission in frog slowly adapting type 1 responses. SomatosensMot Res 27(4):174–185. doi: 10.3109/08990220.2010.516670 CrossRefGoogle Scholar
  51. 51.
    Reinisch CM, Tschachler E (2005) The touch dome in human skin is supplied by different types of nerve fibers. Ann Neurol 58(1):88–95. doi: 10.1002/ana.20527 PubMedCrossRefGoogle Scholar
  52. 52.
    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 PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Senok SS, Baumann KI, Halata Z (1996) Selective phototoxic destruction of quinacrine-loaded Merkel cells is neither selective nor complete. Exp Brain Res 110(3):325–334PubMedCrossRefGoogle Scholar
  54. 54.
    Soya M, Sato M, Sobhan U, Tsumura M, Ichinohe T, Tazaki M, Shibukawa Y (2014) Plasma membrane stretch activates transient receptor potential vanilloid and ankyrin channels in Merkel cells from hamster buccal mucosa. Cell Calcium 55(4):208–218. doi: 10.1016/j.ceca.2014.02.015 PubMedCrossRefGoogle Scholar
  55. 55.
    Tachibana T, Endoh M, Fujiwara N, Nawa T (2005) Receptors and transporter for serotonin in Merkel cell-nerve endings in the rat sinus hair follicle. An Immunohistochemical Study. Arch Histol Cytol 68(1):19–28PubMedCrossRefGoogle Scholar
  56. 56.
    Tachibana T, Nawa T (2002) Recent progress in studies on Merkel cell biology. Anat Sci Int 77(1):26–33. doi: 10.1046/j.0022-7722.2002.00008.x PubMedCrossRefGoogle Scholar
  57. 57.
    Tazaki M, Suzuki T (1998) Calcium inflow of hamster Merkel cells in response to hyposmotic stimulation indicate a stretch activated ion channel. Neurosci Lett 243(1–3):69–72PubMedCrossRefGoogle Scholar
  58. 58.
    van den Pol AN (2012) Neuropeptide transmission in brain circuits. Neuron 76(1):98–115. doi: 10.1016/j.neuron.2012.09.014 PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Van Keymeulen A, Mascre G, Youseff KK, Harel I, Michaux C, De Geest N, Szpalski C, Achouri Y, Bloch W, Hassan BA, Blanpain C (2009) Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis. J Cell Biol 187(1):91–100. doi: 10.1083/jcb.200907080 PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Wellnitz SA, Lesniak DR, Gerling GJ, Lumpkin EA (2010) The regularity of sustained firing reveals two populations of slowly adapting touch receptors in mouse hairy skin. J Neurophysiol 103(6):3378–3388. doi: 10.1152/jn.00810.2009 PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    Woo SH, Ranade S, Weyer AD, Dubin AE, Baba Y, Qiu Z, Petrus M, Miyamoto T, Reddy K, Lumpkin EA, Stucky CL, Patapoutian A (2014) Piezo2 is required for Merkel-cell mechanotransduction. Nature 509:622–626. doi: 10.1038/nature13251 PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Woodbury CJ, Koerber HR (2007) Central and peripheral anatomy of slowly adapting type I low-threshold mechanoreceptors innervating trunk skin of neonatal mice. J Comp Neurol 505(5):547–561. doi: 10.1002/cne.21517 PubMedCrossRefGoogle Scholar
  63. 63.
    Yamashita Y, Akaike N, Wakamori M, Ikeda I, Ogawa H (1992) Voltage-dependent currents in isolated single Merkel cells of rats. J Physiol 450:143–162PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Yamashita Y, Ogawa H (1991) Slowly adapting cutaneous mechanoreceptor afferent units associated with Merkel cells in frogs and effects of direct currents. Somatosens Mot Res 8(1):87–95PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Masashi Nakatani
    • 1
    • 2
  • Srdjan Maksimovic
    • 1
  • Yoshichika Baba
    • 1
  • Ellen A. Lumpkin
    • 1
    • 3
    • 4
  1. 1.Department of DermatologyColumbia UniversityNew YorkUSA
  2. 2.Graduate School of System Design and ManagementKeio UniversityYokohamaJapan
  3. 3.Department of Physiology and Cellular BiophysicsColumbia UniversityNew YorkUSA
  4. 4.Program in Neurobiology and BehaviorColumbia UniversityNew YorkUSA

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