Skip to main content
SpringerLink
Log in

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

  • Chapter
  • First Online:
New Advances in Gastrointestinal Motility Research

Part of the book series: Lecture Notes in Computational Vision and Biomechanics ((LNCVB,volume 10))

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Abriel H (2010) Cardiac sodium channel Na(v)1.5 and interacting proteins: Physiology and pathophysiology. J Mol Cell Cardiol 48(1):2–11

    Article  PubMed  CAS  Google Scholar 

  2. Aldrich RW, Corey DP, Stevens CF (1983) A reinterpretation of mammalian sodium channel gating based on single channel recording. Nature 306(5942):436–441

    Article  PubMed  CAS  Google Scholar 

  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):12–21

    Article  CAS  Google Scholar 

  4. Bennett PB, Yazawa K, Makita N, George AL Jr (1995) Molecular mechanism for an inherited cardiac arrhythmia. Nature 376(6542):683–685

    Article  PubMed  CAS  Google Scholar 

  5. Bennett V, Healy J (2008) Organizing the fluid membrane bilayer: diseases linked to spectrin and ankyrin. Trends Mol Med 14(1):28–36

    Article  PubMed  CAS  Google Scholar 

  6. Beyder A, Farrugia G (2012) Targeting ion channels for the treatment of gastrointestinal motility disorders. Therap Adv Gastroenterol 5(1):5–21

    Article  PubMed  CAS  Google Scholar 

  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):4969–4985

    Google Scholar 

  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):6626–6631

    Article  PubMed  CAS  Google Scholar 

  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, IL

    Google Scholar 

  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):e1000289

    Article  PubMed  Google Scholar 

  11. Buist ML, Corrias A, Poh YC (2010) A model of slow wave propagation and entrainment along the stomach. Ann Biomed Eng 38(9):3022–3030

    Article  PubMed  Google Scholar 

  12. Calabrese B, Tabarean IV, Juranka P, Morris CE (2002) Mechanosensitivity of N-type calcium channel currents. Biophys J 83(5):2560–2574

    Article  PubMed  CAS  Google Scholar 

  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):23–34

    Article  PubMed  CAS  Google Scholar 

  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):137–147

    Article  PubMed  CAS  Google Scholar 

  15. Corrias A, Buist ML (2007) A quantitative model of gastric smooth muscle cellular activation. Ann Biomed Eng 35(9):1595–1607

    Article  PubMed  Google Scholar 

  16. Corrias A, Buist ML (2008) Quantitative cellular description of gastric slow wave activity. Am J Physiol Gastrointest Liver Physiol 294(4):G989–G995

    Article  PubMed  CAS  Google Scholar 

  17. Destexhe A, Huguenard JR (2009) Modeling voltage-dependent channels. In: Schutter ED (ed) Computational modeling methods for neuroscientists. MIT Press, Cambridge, pp 107–137

    Google Scholar 

  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–G680

    Article  PubMed  CAS  Google Scholar 

  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):2784–2792

    Article  PubMed  CAS  Google Scholar 

  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):225–254

    Article  PubMed  Google Scholar 

  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):1772–1781

    Article  Google Scholar 

  22. Dubois JM, Ouanounou G, Rouzaire-Dubois B (2009) The Boltzmann equation in molecular biology. Prog Biophys Mol Biol 99(2–3):87–93

    Article  PubMed  CAS  Google Scholar 

  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):900–905

    Article  PubMed  CAS  Google Scholar 

  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):4834–4852

    Article  PubMed  CAS  Google Scholar 

  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):88–104

    Article  PubMed  CAS  Google Scholar 

  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. 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):15059–15064

    Article  PubMed  CAS  Google Scholar 

  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):450–460

    Article  Google Scholar 

  29. Geiger B, Bershadsky A (2002) Exploring the neighborhood: adhesion-coupled cell mechanosensors. Cell 110(2):139–142

    Article  PubMed  CAS  Google Scholar 

  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):2678–2693

    Article  PubMed  CAS  Google Scholar 

  31. Hille B (2001) Ion channels of excitable membranes, 3rd edn. Sinauer Associates, Inc., Sunderland

    Google Scholar 

  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):500–544

    PubMed  CAS  Google Scholar 

  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):178–187

    Article  PubMed  CAS  Google Scholar 

  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):21413–21418

    Article  PubMed  CAS  Google Scholar 

  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. 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 423:33–41

    Article  PubMed  CAS  Google Scholar 

  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 423:42–48

    Article  PubMed  CAS  Google Scholar 

  38. Keener JP, Sneyd J (2009) Mathematical physiology: cellular physiology. Springer, New York

    Google Scholar 

  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):473–479

    Article  PubMed  CAS  Google Scholar 

  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):547–561

    Article  PubMed  CAS  Google Scholar 

  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):687–701

    Article  PubMed  CAS  Google Scholar 

  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 123:135–154

    Article  PubMed  Google Scholar 

  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 2011

    Google Scholar 

  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 2:29

    Google Scholar 

  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):1299–1304

    Article  PubMed  CAS  Google Scholar 

  46. Long SB, Cambell EB, MacKinnon R (2005) Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science 309(5736):897–903

    Article  PubMed  CAS  Google Scholar 

  47. Long SB, Cambell EB, MacKinnon R (2005) Voltage sensor of Kv1.2: structural basis of electromechanical coupling. Science 309(5736):903–908

    Google Scholar 

  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):376–382

    Article  PubMed  CAS  Google Scholar 

  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):599–621

    Article  PubMed  CAS  Google Scholar 

  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–C1008

    Article  PubMed  CAS  Google Scholar 

  51. Markin VS, Sachs F (2004) Thermodynamics of mechanosensitivity. Phys Biol 1(1–2):110–124

    Article  PubMed  CAS  Google Scholar 

  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):739–758

    Article  PubMed  CAS  Google Scholar 

  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):16537–16544

    Article  PubMed  CAS  Google Scholar 

  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):1080–1085

    Article  PubMed  CAS  Google Scholar 

  55. Morris CE, Juranka PF (2007) Nav channel mechanosensitivity: activation and inactivation accelerate reversibly with stretch. Biophys J 93(3):822–833

    Article  PubMed  CAS  Google Scholar 

  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 442:351–375

    PubMed  CAS  Google Scholar 

  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):3408–3413

    Article  PubMed  CAS  Google Scholar 

  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):477–486

    Article  PubMed  CAS  Google Scholar 

  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):1915–1923

    Article  PubMed  CAS  Google Scholar 

  60. Payandeh J, Scheuer T, Zheng N, Catterall WA (2011) The crystal structure of a voltage-gated sodium channel. Nature 475(7356):353–358

    Google Scholar 

  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):294–304

    Article  PubMed  CAS  Google Scholar 

  62. Poh YC, Beyder A, Strege PR, Farrugia G, Buist ML (2011) Quantification of gastrointestinal sodium channelopathy. J Theor Biol 293C:41–48

    Google Scholar 

  63. Sachs F (2010) Stretch-activated ion channels: what are they? Physiology (Bethesda) 25(1):50–56

    Article  CAS  Google Scholar 

  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–G218

    Article  PubMed  CAS  Google Scholar 

  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, 2009

    Google Scholar 

  66. Scriven DR, Dan P, Moore ED (2000) Distribution of proteins implicated in excitation-contraction coupling in rat ventricular myocytes. Biophys J 79(5):2682–2691

    Article  PubMed  CAS  Google Scholar 

  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):e12196

    Article  PubMed  Google Scholar 

  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):402–413

    Article  PubMed  CAS  Google Scholar 

  69. Smirnov SV, Zholos AV, Shuba MF (1992) Potential-dependent inward currents in single isolated smooth muscle cells of the rat ileum. J Physiol 454:549–571

    PubMed  CAS  Google Scholar 

  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–C66

    Article  PubMed  CAS  Google Scholar 

  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):135–143

    Article  PubMed  CAS  Google Scholar 

  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–G1121

    PubMed  CAS  Google Scholar 

  73. Suchyna TM, Markin VS, Sachs F (2009) Biophysics and structure of the patch and the gigaseal. Biophys J 97(3):738–747

    Article  PubMed  CAS  Google Scholar 

  74. Tabarean IV, Juranka P, Morris CE (1999) Membrane stretch affects gating modes of a skeletal muscle sodium channel. Biophys J 77(2):758–774

    Article  PubMed  CAS  Google Scholar 

  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):2982–2994

    Article  PubMed  CAS  Google Scholar 

  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):107–115

    Google Scholar 

  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):592–595

    Article  PubMed  CAS  Google Scholar 

  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–H214

    PubMed  CAS  Google Scholar 

  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):2104–2112

    Article  PubMed  CAS  Google Scholar 

  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):207–218

    Article  PubMed  CAS  Google Scholar 

  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):14913–14918

    Article  PubMed  CAS  Google Scholar 

  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):485–491

    Article  PubMed  CAS  Google Scholar 

  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):443–449

    Article  PubMed  CAS  Google Scholar 

  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):1135–1154

    Article  PubMed  CAS  Google Scholar 

  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):4905–4918

    Google Scholar 

Download references

Acknowledgments

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

Author information

Authors and Affiliations

  1. Enteric Neuroscience Program and Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA

    Arthur Beyder & Gianrico Farrugia

  2. Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand

    Rachel Lees-Green

Authors
  1. Arthur Beyder
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rachel Lees-Green
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gianrico Farrugia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arthur Beyder .

Editor information

Editors and Affiliations

  1. , Auckland Bioengineering Institute, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand

    L. K. Cheng

  2. , Auckland Bioengineering Institute, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand

    A. J. Pullan

  3. The Mayo Clinic, First Street SW 200, Rochester, 55905, Minnesota, USA

    G. Farrugia

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Beyder, A., Lees-Green, R., Farrugia, G. (2013). Role of Ion Channel Mechanosensitivity in the Gut: Mechano-Electrical Feedback Exemplified By Stretch-Dependence of Nav1.5. In: Cheng, L., Pullan, A., Farrugia, G. (eds) New Advances in Gastrointestinal Motility Research. Lecture Notes in Computational Vision and Biomechanics, vol 10. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6561-0_2

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-6561-0_2

  • Published:

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-007-6560-3

  • Online ISBN: 978-94-007-6561-0

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics

Search

Navigation