Role of Ion Channel Mechanosensitivity in the Gut: Mechano-Electrical Feedback Exemplified By Stretch-Dependence of Nav1.5

  • Arthur Beyder
  • Rachel Lees-Green
  • Gianrico Farrugia
Part of the Lecture Notes in Computational Vision and Biomechanics book series (LNCVB, volume 10)


NaV1.5 is a voltage-gated sodium channel found in the human gastrointestinal tract. In smooth muscle cells (SMC) and interstitial cells of Cajal (ICC), NaV1.5 regulates the resting potential as well as slow wave upstroke and frequency. Mutations in SCN5A, the gene coding for NaV1.5, are associated with gastrointestinal functional disorders. Some patients with irritable bowel syndrome (IBS) have SCN5A mutations that result in functionally abnormal channels. NaV1.5 is mechanosensitive, and some of the mutations associated with gastrointestinal (GI) motility disorders have impaired mechanosensitivity. NaV1.5 mechanosensitivity involves the actin cytoskeleton and associating proteins as well as the lipid bilayer. Mechanical stimulation of NaV1.5 results in an increase in peak current, acceleration of the voltage-dependent activation & inactivation and slowed recovery from inactivation. Biophysical modeling is increasingly used as a tool for investigating the effect of NaV1.5 and other mechanosensitive components in slow wave generation. We summarize the existing models of gastrointestinal cellular electrical activity, and specifically a model of NaV1.5 mechanosensitivity that has been incorporated into one of the cell models. In agreement with the experimental data, mechanical stimulation of NaV1.5 results in increased excitability of the cell model in silico. In this chapter we discuss the current knowledge of the molecular mechanism of NaV1.5 mechanosensitivity, mechano-electrical consequences of NaV1.5 stretch in cells and propose physiologic and pathophysiologic consequences.


Irritable Bowel Syndrome Slow Wave Irritable Bowel Syndrome Patient Gastric Electrical Stimulation Voltage Sensor Domain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Work supported in part by a grant from the NIH (R01 DK52766) (GF) and American Physiological Society Career Enhancement Award (AB).


  1. 1.
    Abriel H (2010) Cardiac sodium channel Na(v)1.5 and interacting proteins: Physiology and pathophysiology. J Mol Cell Cardiol 48(1):2–11PubMedCrossRefGoogle Scholar
  2. 2.
    Aldrich RW, Corey DP, Stevens CF (1983) A reinterpretation of mammalian sodium channel gating based on single channel recording. Nature 306(5942):436–441PubMedCrossRefGoogle Scholar
  3. 3.
    Banderali U, Juranka PF, Clark RB, Giles WR, Morris CE (2010) Impaired stretch modulation in potentially lethal cardiac sodium channel mutants. Channels (Austin) 4(1):12–21CrossRefGoogle Scholar
  4. 4.
    Bennett PB, Yazawa K, Makita N, George AL Jr (1995) Molecular mechanism for an inherited cardiac arrhythmia. Nature 376(6542):683–685PubMedCrossRefGoogle Scholar
  5. 5.
    Bennett V, Healy J (2008) Organizing the fluid membrane bilayer: diseases linked to spectrin and ankyrin. Trends Mol Med 14(1):28–36PubMedCrossRefGoogle Scholar
  6. 6.
    Beyder A, Farrugia G (2012) Targeting ion channels for the treatment of gastrointestinal motility disorders. Therap Adv Gastroenterol 5(1):5–21PubMedCrossRefGoogle Scholar
  7. 7.
    Beyder A, Rae, JL, Bernard, C, Strege, PR, Sachs, F, Farrugia, G (2010) Mechanosensitivity of Nav1.5, a voltage-sensitive sodium channel. J Physiol 588(24):4969–4985Google Scholar
  8. 8.
    Beyder A, Sachs F (2009) Electromechanical coupling in the membranes of Shaker-transfected HEK cells. Proc Natl Acad Sci U S A 106(16):6626–6631PubMedCrossRefGoogle Scholar
  9. 9.
    Beyder A, Strege P, Mazzone A, Bernard C, Tester DJ, Saito YA, Ackerman M, Farrugia G (2011) Mutations in SCN5A from patients with IBS result in abnormal Nav1.5 function. Digestive Diseases Week, Chicago, ILGoogle Scholar
  10. 10.
    Bjelkmar P, Niemela PS, Vattulainen I, Lindahl E (2009) Conformational changes and slow dynamics through microsecond polarized atomistic molecular simulation of an integral Kv1.2 ion channel. PLoS Comput Biol 5(2):e1000289PubMedCrossRefGoogle Scholar
  11. 11.
    Buist ML, Corrias A, Poh YC (2010) A model of slow wave propagation and entrainment along the stomach. Ann Biomed Eng 38(9):3022–3030PubMedCrossRefGoogle Scholar
  12. 12.
    Calabrese B, Tabarean IV, Juranka P, Morris CE (2002) Mechanosensitivity of N-type calcium channel currents. Biophys J 83(5):2560–2574PubMedCrossRefGoogle Scholar
  13. 13.
    Conti F, Fioravanti R, Segal JR, Stuhmer W (1982) Pressure dependence of the sodium currents of squid giant axon. J Membr Biol 69(1):23–34PubMedCrossRefGoogle Scholar
  14. 14.
    Conti F, Inoue I, Kukita F, Stuhmer W (1984) Pressure dependence of sodium gating currents in the squid giant axon. Eur Biophys J 11(2):137–147PubMedCrossRefGoogle Scholar
  15. 15.
    Corrias A, Buist ML (2007) A quantitative model of gastric smooth muscle cellular activation. Ann Biomed Eng 35(9):1595–1607PubMedCrossRefGoogle Scholar
  16. 16.
    Corrias A, Buist ML (2008) Quantitative cellular description of gastric slow wave activity. Am J Physiol Gastrointest Liver Physiol 294(4):G989–G995PubMedCrossRefGoogle Scholar
  17. 17.
    Destexhe A, Huguenard JR (2009) Modeling voltage-dependent channels. In: Schutter ED (ed) Computational modeling methods for neuroscientists. MIT Press, Cambridge, pp 107–137Google Scholar
  18. 18.
    Du P, Li S, O’Grady G, Cheng LK, Pullan AJ, Chen JD (2009) Effects of electrical stimulation on isolated rodent gastric smooth muscle cells evaluated via a joint computational simulation and experimental approach. Am J Physiol Gastrointest Liver Physiol 297(4):G672–G680PubMedCrossRefGoogle Scholar
  19. 19.
    Du P, O’Grady G, Cheng LK, Pullan AJ (2010) A multiscale model of the electrophysiological basis of the human electrogastrogram. Biophys J 99(9):2784–2792PubMedCrossRefGoogle Scholar
  20. 20.
    Du P, O’Grady G, Davidson JB, Cheng LK, Pullan AJ (2010) Multiscale modeling of gastrointestinal electrophysiology and experimental validation. Crit Rev Biomed Eng 38(3):225–254PubMedCrossRefGoogle Scholar
  21. 21.
    Du P, O’Grady G, Gibbons SJ, Yassi R, Lees-Green R, Farrugia G, Cheng LK, Pullan AJ (2009) Tissue-specific mathematical models of slow wave entrainment in wild-type and 5-HT(2B) knockout mice with altered interstitial cells of Cajal networks. Biophys J 98(9):1772–1781CrossRefGoogle Scholar
  22. 22.
    Dubois JM, Ouanounou G, Rouzaire-Dubois B (2009) The Boltzmann equation in molecular biology. Prog Biophys Mol Biol 99(2–3):87–93PubMedCrossRefGoogle Scholar
  23. 23.
    Farrugia G, Holm AN, Rich A, Sarr MG, Szurszewski JH, Rae JL (1999) A mechanosensitive calcium channel in human intestinal smooth muscle cells. Gastroenterology 117(4):900–905PubMedCrossRefGoogle Scholar
  24. 24.
    Faville RA, Pullan AJ, Sanders KM, Koh SD, Lloyd CM, Smith NP (2009) Biophysically based mathematical modeling of interstitial cells of Cajal slow wave activity generated from a discrete unitary potential basis. Biophys J 96(12):4834–4852PubMedCrossRefGoogle Scholar
  25. 25.
    Faville RA, Pullan AJ, Sanders KM, Smith NP (2008) A biophysically based mathematical model of unitary potential activity in interstitial cells of Cajal. Biophys J 95(1):88–104PubMedCrossRefGoogle Scholar
  26. 26.
    Fernandez-Tenorio M, Gonzalez-Rodriguez P, Porras C, Castellano A, Moosmang S, Hofmann F, Urena J, Lopez-Barneo J (2010) Short communication: genetic ablation of L-type Ca2+ channels abolishes depolarization-induced Ca2+ release in arterial smooth muscle. Circ Res 106(7):1285–1289 Google Scholar
  27. 27.
    Freites JA, Tobias DJ, von Heijne G, White SH (2005) Interface connections of a transmembrane voltage sensor. Proc Natl Acad Sci U S A 102(42):15059–15064PubMedCrossRefGoogle Scholar
  28. 28.
    Gajendiran V, Buist ML (2011) A quantitative description of active force generation in gastrointestinal smooth muscle. Int J Numer Methods Biomed Eng 27(3):450–460CrossRefGoogle Scholar
  29. 29.
    Geiger B, Bershadsky A (2002) Exploring the neighborhood: adhesion-coupled cell mechanosensors. Cell 110(2):139–142PubMedCrossRefGoogle Scholar
  30. 30.
    Gu CX, Juranka PF, Morris CE (2001) Stretch-activation and stretch-inactivation of Shaker-IR, a voltage-gated K+ channel. Biophys J 80(6):2678–2693PubMedCrossRefGoogle Scholar
  31. 31.
    Hille B (2001) Ion channels of excitable membranes, 3rd edn. Sinauer Associates, Inc., SunderlandGoogle Scholar
  32. 32.
    Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 117(4):500–544PubMedGoogle Scholar
  33. 33.
    Holm AN, Rich A, Miller SM, Strege P, Ou Y, Gibbons S, Sarr MG, Szurszewski JH, Rae JL, Farrugia G (2002) Sodium current in human jejunal circular smooth muscle cells. Gastroenterology 122(1):178–187PubMedCrossRefGoogle Scholar
  34. 34.
    Huang F, Rock JR, Harfe BD, Cheng T, Huang X, Jan YN, Jan LY (2009) Studies on expression and function of the TMEM16A calcium-activated chloride channel. Proc Natl Acad Sci U S A 106(50):21413–21418PubMedCrossRefGoogle Scholar
  35. 35.
    Hwang SJ, Blair PJ, Britton FC, Odriscoll KE, Hennig G, Bayguinov JR, Rock JR, Harfe BD, Sanders KM, Ward SM (2009) Expression of anoctamin 1/TMEM16A by interstitial cells of Cajal is fundamental for slow wave activity in gastrointestinal muscles. J Physiol 587(20):4887–4904 Google Scholar
  36. 36.
    Jiang Y, Lee A, Chen J, Ruta V, Cadene M, Chait BT, MacKinnon R (2003) X-ray structure of a voltage-dependent K+ channel. Nature 423:33–41PubMedCrossRefGoogle Scholar
  37. 37.
    Jiang Y, Ruta V, Chen J, Lee A, MacKinnon R (2003) The principle of gating charge movement in a voltage-dependent K+ channel. Nature 423:42–48PubMedCrossRefGoogle Scholar
  38. 38.
    Keener JP, Sneyd J (2009) Mathematical physiology: cellular physiology. Springer, New YorkGoogle Scholar
  39. 39.
    Krepkiy D, Mihailescu M, Freites JA, Schow EV, Worcester DL, Gawrisch K, Tobias DJ, White SH, Swartz KJ (2009) Structure and hydration of membranes embedded with voltage-sensing domains. Nature 462(7272):473–479PubMedCrossRefGoogle Scholar
  40. 40.
    Kunze WA, Clerc N, Bertrand PP, Furness JB (1999) Contractile activity in intestinal muscle evokes action potential discharge in guinea-pig myenteric neurons. J Physiol 517(2):547–561PubMedCrossRefGoogle Scholar
  41. 41.
    Laitko U, Juranka PF, Morris CE (2006) Membrane stretch slows the concerted step prior to opening in a Kv channel. J Gen Physiol 127(6):687–701PubMedCrossRefGoogle Scholar
  42. 42.
    Laitko U, Morris CE (2004) Membrane tension accelerates rate-limiting voltage-dependent activation and slow inactivation steps in a Shaker channel. J Gen Physiol 123:135–154PubMedCrossRefGoogle Scholar
  43. 43.
    Lees-Green R, Beyder A, Farrugia G, O'Grady G, Poh YC, Buist ML, Pullan AJ (2011) Computational modeling of the sodium channel mechanical stretch effects on the electrical function of human interstitial cells of Cajal and smooth muscle cells. Digestive Diseases Week, Chicago, IL, May 2011Google Scholar
  44. 44.
    Lees-Green R, Du P, O'Grady G, Beyder A, Farrugia G, Pullan AJ (2011) Biophysically-based modelling of the interstitial cells of Cajal: Current status and future perspectives. Frontiers Comput Physiol Med 2:29Google Scholar
  45. 45.
    Locke GR 3rd, Ackerman MJ, Zinsmeister AR, Thapa P, Farrugia G (2006) Gastrointestinal symptoms in families of patients with an SCN5A-encoded cardiac channelopathy: evidence of an intestinal channelopathy. Am J Gastroenterol 101(6):1299–1304PubMedCrossRefGoogle Scholar
  46. 46.
    Long SB, Cambell EB, MacKinnon R (2005) Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science 309(5736):897–903PubMedCrossRefGoogle Scholar
  47. 47.
    Long SB, Cambell EB, MacKinnon R (2005) Voltage sensor of Kv1.2: structural basis of electromechanical coupling. Science 309(5736):903–908Google Scholar
  48. 48.
    Long SB, Tao X, Campbell EB, MacKinnon R (2007) Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment. Nature 450(7168):376–382PubMedCrossRefGoogle Scholar
  49. 49.
    Lundbaek JA, Birn P, Hansen AJ, Sogaard R, Nielsen C, Girshman J, Bruno MJ, Tape SE, Egebjerg J, Greathouse DV, Mattice GL, Koeppe RE 2nd, Andersen OS (2004) Regulation of sodium channel function by bilayer elasticity: the importance of hydrophobic coupling. Effects of Micelle-forming amphiphiles and cholesterol. J Gen Physiol 123(5):599–621PubMedCrossRefGoogle Scholar
  50. 50.
    Lyford GL, Strege PR, Shepard A, Ou Y, Ermilov L, Miller SM, Gibbons SJ, Rae JL, Szurszewski JH, Farrugia G (2002) Alpha(1C) (Ca(V)1.2) L-type calcium channel mediates mechanosensitive calcium regulation. Am J Physiol Cell Physiol 283(3):C1001–C1008PubMedCrossRefGoogle Scholar
  51. 51.
    Markin VS, Sachs F (2004) Thermodynamics of mechanosensitivity. Phys Biol 1(1–2):110–124PubMedCrossRefGoogle Scholar
  52. 52.
    Matteson DR, Armstrong CM (1982) Evidence for a population of sleepy sodium channels in squid axon at low temperature. J Gen Physiol 79(5):739–758PubMedCrossRefGoogle Scholar
  53. 53.
    Mazzone A, Strege PR, Tester DJ, Bernard CE, Faulkner G, De Giorgio R, Makielski JC, Stanghellini V, Gibbons SJ, Ackerman MJ, Farrugia G (2008) A mutation in telethonin alters Nav1.5 function. J Biol Chem 283(24):16537–16544PubMedCrossRefGoogle Scholar
  54. 54.
    Milescu M, Bosmans F, Lee S, Alabi AA, Kim JI, Swartz KJ (2009) Interactions between lipids and voltage sensor paddles detected with tarantula toxins. Nat Struct Mol Biol 16(10):1080–1085PubMedCrossRefGoogle Scholar
  55. 55.
    Morris CE, Juranka PF (2007) Nav channel mechanosensitivity: activation and inactivation accelerate reversibly with stretch. Biophys J 93(3):822–833PubMedCrossRefGoogle Scholar
  56. 56.
    Muraki K, Imaizumi Y, Watanabe M (1991) Sodium currents in smooth muscle cells freshly isolated from stomach fundus of the rat and ureter of the guinea-pig. J Physiol 442:351–375PubMedGoogle Scholar
  57. 57.
    Nozawa K, Kawabata-Shoda E, Doihara H, Kojima R, Okada H, Mochizuki S, Sano Y, Inamura K, Matsushime H, Koizumi T, Yokoyama T, Ito H (2009) TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells. Proc Natl Acad Sci U S A 106(9):3408–3413PubMedCrossRefGoogle Scholar
  58. 58.
    Ou Y, Gibbons SJ, Miller SM, Strege PR, Rich A, Distad MA, Ackerman MJ, Rae JL, Szurszewski JH, Farrugia G (2002) SCN5A is expressed in human jejunal circular smooth muscle cells. Neurogastroenterol Motil 14(5):477–486PubMedCrossRefGoogle Scholar
  59. 59.
    Ou Y, Strege P, Miller SM, Makielski J, Ackerman M, Gibbons SJ, Farrugia G (2003) Syntrophin gamma 2 regulates SCN5A gating by a PDZ domain-mediated interaction. J Biol Chem 278(3):1915–1923PubMedCrossRefGoogle Scholar
  60. 60.
    Payandeh J, Scheuer T, Zheng N, Catterall WA (2011) The crystal structure of a voltage-gated sodium channel. Nature 475(7356):353–358Google Scholar
  61. 61.
    Petitprez S, Zmoos AF, Ogrodnik J, Balse E, Raad N, El-Haou S, Albesa M, Bittihn P, Luther S, Lehnart SE, Hatem SN, Coulombe A, Abriel H (2011) SAP97 and dystrophin macromolecular complexes determine two pools of cardiac sodium channels Nav1.5 in cardiomyocytes. Circ Res 108(3):294–304PubMedCrossRefGoogle Scholar
  62. 62.
    Poh YC, Beyder A, Strege PR, Farrugia G, Buist ML (2011) Quantification of gastrointestinal sodium channelopathy. J Theor Biol 293C:41–48Google Scholar
  63. 63.
    Sachs F (2010) Stretch-activated ion channels: what are they? Physiology (Bethesda) 25(1):50–56CrossRefGoogle Scholar
  64. 64.
    Saito YA, Strege PR, Tester DJ, Locke GR 3rd, Talley NJ, Bernard CE, Rae JL, Makielski JC, Ackerman MJ, Farrugia G (2009) Sodium channel mutation in irritable bowel syndrome: evidence for an ion channelopathy. Am J Physiol Gastrointest Liver Physiol 296(2):G211–G218PubMedCrossRefGoogle Scholar
  65. 65.
    Saito YA, Tester DJ, Mazzone A, Beyder A, Locke GR, 3rd, Talley NJ, Ackerman M, Farrugia G (2009) Sodium channel mutations in irritable bowel syndrome. Neurogastroenterology & Motility, Chicago, IL, 2009Google Scholar
  66. 66.
    Scriven DR, Dan P, Moore ED (2000) Distribution of proteins implicated in excitation-contraction coupling in rat ventricular myocytes. Biophys J 79(5):2682–2691PubMedCrossRefGoogle Scholar
  67. 67.
    Shi ZD, Abraham G, Tarbell JM (2010) Shear stress modulation of smooth muscle cell marker genes in 2-D and 3-D depends on mechanotransduction by heparan sulfate proteoglycans and ERK1/2. PLoS One 5(8):e12196PubMedCrossRefGoogle Scholar
  68. 68.
    Sinha B, Koster D, Ruez R, Gonnord P, Bastiani M, Abankwa D, Stan RV, Butler-Browne G, Vedie B, Johannes L, Morone N, Parton RG, Raposo G, Sens P, Lamaze C, Nassoy P (2011) Cells respond to mechanical stress by rapid disassembly of caveolae. Cell 144(3):402–413PubMedCrossRefGoogle Scholar
  69. 69.
    Smirnov SV, Zholos AV, Shuba MF (1992) Potential-dependent inward currents in single isolated smooth muscle cells of the rat ileum. J Physiol 454:549–571PubMedGoogle Scholar
  70. 70.
    Strege PR, Holm AN, Rich A, Miller SM, Ou Y, Sarr MG, Farrugia G (2003) Cytoskeletal modulation of sodium current in human jejunal circular smooth muscle cells. Am J Physiol Cell Physiol 284(1):C60–C66PubMedCrossRefGoogle Scholar
  71. 71.
    Strege PR, Mazzone A, Kraichely RE, Sha L, Holm AN, Ou Y, Lim I, Gibbons SJ, Sarr MG, Farrugia G (2007) Species dependent expression of intestinal smooth muscle mechanosensitive sodium channels. Neurogastroenterol Motil 19(2):135–143PubMedCrossRefGoogle Scholar
  72. 72.
    Strege PR, Ou Y, Sha L, Rich A, Gibbons SJ, Szurszewski JH, Sarr MG, Farrugia G (2003) Sodium current in human intestinal interstitial cells of Cajal. Am J Physiol Gastrointest Liver Physiol 285(6):G1111–G1121PubMedGoogle Scholar
  73. 73.
    Suchyna TM, Markin VS, Sachs F (2009) Biophysics and structure of the patch and the gigaseal. Biophys J 97(3):738–747PubMedCrossRefGoogle Scholar
  74. 74.
    Tabarean IV, Juranka P, Morris CE (1999) Membrane stretch affects gating modes of a skeletal muscle sodium channel. Biophys J 77(2):758–774PubMedCrossRefGoogle Scholar
  75. 75.
    Tabarean IV, Morris CE (2002) Membrane stretch accelerates activation and slow inactivation in Shaker channels with S3–S4 linker deletions. Biophys J 82(6):2982–2994PubMedCrossRefGoogle Scholar
  76. 76.
    Tfelt-Hansen J, Winkel BG, Grunnet M, Jespersen T (2010) Inherited cardiac diseases caused by mutations in the Nav1.5 sodium channel. J Cardiovasc Electrophysiol 21(1):107–115Google Scholar
  77. 77.
    Trepat X, Deng L, An SS, Navajas D, Tschumperlin DJ, Gerthoffer WT, Butler JP, Fredberg JJ (2007) Universal physical responses to stretch in the living cell. Nature 447(7144):592–595PubMedCrossRefGoogle Scholar
  78. 78.
    Undrovinas AI, Shander GS, Makielski JC (1995) Cytoskeleton modulates gating of voltage-dependent sodium channel in heart. Am J Physiol 269(1 Pt 2):H203–H214PubMedGoogle Scholar
  79. 79.
    Vatta M, Ackerman MJ, Ye B, Makielski JC, Ughanze EE, Taylor EW, Tester DJ, Balijepalli RC, Foell JD, Li Z, Kamp TJ, Towbin JA (2006) Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome. Circulation 114(20):2104–2112PubMedCrossRefGoogle Scholar
  80. 80.
    Ward SM, Baker SA, de Faoite A, Sanders KM (2003) Propagation of slow waves requires IP3 receptors and mitochondrial Ca2+ uptake in canine colonic muscles. J Physiol 549(1):207–218PubMedCrossRefGoogle Scholar
  81. 81.
    Won KJ, Sanders KM, Ward SM (2005) Interstitial cells of Cajal mediate mechanosensitive responses in the stomach. Proc Natl Acad Sci U S A 102(41):14913–14918PubMedCrossRefGoogle Scholar
  82. 82.
    Xiong Z, Sperelakis N, Noffsinger A, Fenoglio-Preiser C (1993) Fast Na+ current in circular smooth muscle cells of the large intestine. Pflugers Arch 423(5–6):485–491PubMedCrossRefGoogle Scholar
  83. 83.
    Yarbrough TL, Lu T, Lee HC, Shibata EF (2002) Localization of cardiac sodium channels in caveolin-rich membrane domains: regulation of sodium current amplitude. Circ Res 90(4):443–449PubMedCrossRefGoogle Scholar
  84. 84.
    Youm JB, Kim N, Han J, Kim E, Joo H, Leem CH, Goto G, Noma A, Earm YE (2006) A mathematical model of pacemaker activity recorded from mouse small intestine. Philos Trans A Math Phys Eng Sci 364(1842):1135–1154PubMedCrossRefGoogle Scholar
  85. 85.
    Zhu MH, Kim TW, Ro S, Yan W, Ward SM, Koh SD, Sanders KM (2009) A Ca2+-activated Cl- conductance in interstitial cells of Cajal linked to slow wave currents and pacemaker activity. J Physiol 587(20):4905–4918Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Arthur Beyder
    • 1
  • Rachel Lees-Green
    • 2
  • Gianrico Farrugia
    • 1
  1. 1.Enteric Neuroscience Program and Division of Gastroenterology and HepatologyMayo ClinicRochesterUSA
  2. 2.Auckland Bioengineering InstituteThe University of AucklandAucklandNew Zealand

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