Skip to main content
SpringerLink
Log in

ICC Network Density: Regulation and Consequences

  • 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

Interstitial cells of Cajal (ICC) are mesoderm-derived mesenchymal cells found in the smooth muscle layers of the gastrointestinal tract. They contribute to the normal function of the gut by generating rhythmic electrical activity, as intermediaries in neuromuscular signalling, altering the membrane potential of adjacent smooth muscle and responding to mechanical stretch. Depletion of ICC is associated with several gastrointestinal motility disorders including diabetic gastroparesis, slow transit constipation and intestinal pseudo-obstruction. This chapter reviews the information that can be obtained from measuring and characterizing networks of interstitial cells of Cajal in health and disease, the applications of that information in computer modelling and about how mathematical modelling might inform further efforts to characterize and/or reverse ICC network depletion. We describe the appropriate techniques for tissue collection and handling when investigating effects on ICC networks. Methods for identifying, accurately quantifying and mapping ICC are presented together with new analyses that can identify changes to the geometry as well as the density of the ICC networks. Finally we discuss the information that is obtained on the relationship between ICC network changes and alterations to gastrointestinal function and show how computer modelling of virtual ICC networks could be used to predict those relationships.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
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. Alberti E, Mikkelsen HB, Larsen JO, Jimenez M (2005) Motility patterns and distribution of interstitial cells of Cajal and nitrergic neurons in the proximal, mid- and distal-colon of the rat. Neurogastroenterol Motil 17:133–147

    Article  PubMed  CAS  Google Scholar 

  2. Bernard CE, Gibbons SJ, Gomez-Pinilla PJ, Lurken MS, Schmalz PF, Roeder JL, Linden D, Cima RR, Dozois EJ, Larson DW, Camilleri M, Zinsmeister AR, Pozo MJ, Hicks GA, Farrugia G (2009) Effect of age on the enteric nervous system of the human colon. Neurogastroenterol Motil 21:746–e746

    Article  PubMed  CAS  Google Scholar 

  3. Bolton TB, Gordienko DV, Povstyan OV, Harhun MI, Pucovsky V (2004) Smooth muscle cells and interstitial cells of blood vessels. Cell Calcium 35:643–657

    Article  PubMed  CAS  Google Scholar 

  4. Burns AJ, Lomax AE, Torihashi S, Sanders KM, Ward SM (1996) Interstitial cells of Cajal mediate inhibitory neurotransmission in the stomach. Proc Natl Acad Sci USA 93:12008–12013

    Article  PubMed  CAS  Google Scholar 

  5. Chen H, Redelman D, Ro S, Ward SM, Ordog T, Sanders KM (2007) Selective labeling and isolation of functional classes of interstitial cells of Cajal of human and murine small intestine. Am J Physiol Cell Physiol 292:C497–C507

    Article  PubMed  CAS  Google Scholar 

  6. Choi KM, Gibbons SJ, Nguyen TV, Stoltz GJ, Lurken MS, Ordog T, Szurszewski JH, Farrugia G (2008) Heme oxygenase-1 protects interstitial cells of Cajal from oxidative stress and reverses diabetic gastroparesis. Gastroenterology 135:2055–2064

    Article  PubMed  CAS  Google Scholar 

  7. Choi KM, Gibbons SJ, Roeder JL, Lurken MS, Zhu J, Wouters MM, Miller SM, Szurszewski JH, Farrugia G (2007) Regulation of interstitial cells of Cajal in the mouse gastric body by neuronal nitric oxide. Neurogastroenterol Motil 19:585–595

    Article  PubMed  CAS  Google Scholar 

  8. Christensen J, Rick GA, Lowe LS (1992) Distributions of interstitial cells of Cajal in stomach and colon of cat, dog, ferret, opossum, rat, guinea pig and rabbit. J Auton Nerv Syst 37:47–56

    Article  PubMed  CAS  Google Scholar 

  9. Espinosa I, Lee CH, Kim MK, Rouse BT, Subramanian S, Montgomery K, Varma S, Corless CL, Heinrich MC, Smith KS, Wang Z, Rubin B, Nielsen TO, Seitz RS, Ross DT, West RB, Cleary ML, van de Rijn M (2008) A novel monoclonal antibody against DOG1 is a sensitive and specific marker for gastrointestinal stromal tumors. Am J Surg Pathol 32:210–218

    Article  PubMed  Google Scholar 

  10. Farrugia G (2008) Interstitial cells of Cajal in health and disease. Neurogastroenterol Motil 20(Suppl 1):54–63

    Article  PubMed  Google Scholar 

  11. Farrugia G, Lei S, Lin X, Miller SM, Nath KA, Ferris CD, Levitt M, Szurszewski JH (2003) A major role for carbon monoxide as an endogenous hyperpolarizing factor in the gastrointestinal tract. Proc Natl Acad Sci USA 100:8567–8570

    Article  PubMed  CAS  Google Scholar 

  12. Feldstein AE, Miller SM, El-Youssef M, Rodeberg D, Lindor NM, Burgart LJ, Szurszewski JH, Farrugia G (2003) Chronic intestinal pseudoobstruction associated with altered interstitial cells of Cajal networks. J Pediatr Gastroenterol Nutr 36:492–497

    Article  PubMed  Google Scholar 

  13. Fu YY, Lin CW, Enikolopov G, Sibley E, Chiang AS, Tang SC (2009) Microtome-free 3-dimensional confocal imaging method for visualization of mouse intestine with subcellular-level resolution. Gastroenterology 137:453–465

    Article  PubMed  Google Scholar 

  14. Gao J, Du P, Archer R, O'Grady G, Gibbons SJ, Farrugia G, Cheng LK, Pullan AJ (2011) A stochastic multi-scale model of electrical function in normal and depleted ICC networks. IEEE Trans Bio-Med Eng 58:3451–3455. doi:10.1109/TBME.2011.2164248

    Article  Google Scholar 

  15. Gao J, Du P, Archer R, Gibbons SJ, O’Grady G, Farrugia G, Pullan AJ (2011) Virtual ICC network generation algorithms for modeling the physiological consequences of ICC depletion. Gastroenterology 140:S-373

    Google Scholar 

  16. Garrity MM, Burgart LJ, Mahoney MR, Windschitl HE, Salim M, Wiesenfeld M, Krook JE, Michalak JC, Goldberg RM, O’Connell MJ, Furth AF, Sargent DJ, Murphy LM, Hill E, Riehle DL, Meyers CH, Witzig TE, North Central Cancer Treatment Group (2004) Prognostic value of proliferation, apoptosis, defective DNA mismatch repair, and p53 overexpression in patients with resected Dukes’ B2 or C colon cancer: a North Central Cancer Treatment Group Study. J Clin Oncol 22:1572–1582

    Google Scholar 

  17. Garrity MM, Gibbons SJ, Smyrk TC, Vanderwinden JM, Gomez-Pinilla PJ, Nehra A, Borg M, Farrugia G (2009) Diagnostic challenges of motility disorders: optimal detection of CD117+ interstitial cells of Cajal. Histopathology 54:286–294

    Article  PubMed  Google Scholar 

  18. Gibbons SJ, De Giorgio R, Pellegrini MS, Garrity-Park MM, Miller SM, Schmalz PF, Young-Fadok TM, Larson DW, Dozois EJ, Camilleri M, Stanghellini V, Szurszewski JH, Farrugia G (2009) Apoptotic cell death of human interstitial cells of Cajal. Neurogastroenterol Motil 21:85–93. doi:10.1111/j.1365-2982.2008.01185.x

    Article  PubMed  CAS  Google Scholar 

  19. Gomez-Pinilla PJ, Gibbons SJ, Bardsley MR, Lorincz A, Pozo MJ, Pasricha PJ, Van de Rijn M, West RB, Sarr MG, Kendrick ML, Cima RR, Dozois EJ, Larson DW, Ordog T, Farrugia G (2009) Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol 296:G1370–G1381

    Article  PubMed  CAS  Google Scholar 

  20. Gomez-Pinilla PJ, Gibbons SJ, Sarr MG, Kendrick ML, Shen KR, Cima RR, Dozois EJ, Larson DW, Ordog T, Pozo MJ, Farrugia G (2011) Changes in interstitial cells of Cajal with age in the human stomach and colon. Neurogastroenterol Motil 23:36–44

    Article  PubMed  CAS  Google Scholar 

  21. Grover M, Bernard CE, Pasricha PJ, Lurken MS, Faussone-Pellegrini MS, Smyrk TC, Parkman HP, Abell TL, Snape WJ, Hasler WL, McCallum RW, Nguyen L, Koch KL, Calles J, Lee L, Tonascia J, Unalp-Arida A, Hamilton FA, Farrugia G (2012) Clinical-histological associations in gastroparesis: results from the Gastroparesis Clinical Research Consortium. Neurogastroenterol Motil 24(6)531–9, e249

    Google Scholar 

  22. Grover M, Farrugia G, Lurken MS, Bernard CE, Faussone-Pellegrini MS, Smyrk TC, Parkman HP, Abell TL, Snape WJ, Hasler WL, Unalp-Arida A, Nguyen L, Koch KL, Calles J, Lee L, Tonascia J, Hamilton FA, Pasricha PJ, NIDDK Gastroparesis Clinical Research Consortium (2011) Cellular changes in diabetic and idiopathic gastroparesis. Gastroenterology 140:1575–85.e8

    Google Scholar 

  23. He CL, Burgart L, Wang L, Pemberton J, Young-Fadok T, Szurszewski J, Farrugia G (2000) Decreased interstitial cell of Cajal volume in patients with slow-transit constipation. Gastroenterology 118:14–21

    Article  PubMed  CAS  Google Scholar 

  24. He CL, Soffer EE, Ferris CD, Walsh RM, Szurszewski JH, Farrugia G (2001) Loss of interstitial cells of Cajal and inhibitory innervation in insulin-dependent diabetes. Gastroenterology 121:427–434

    Article  PubMed  CAS  Google Scholar 

  25. Horiguchi K, Komuro T (2000) Ultrastructural observations of fibroblast-like cells forming gap junctions in the W/W(nu) mouse small intestine. J Auton Nerv Syst 80:142–147

    Article  PubMed  CAS  Google Scholar 

  26. Huizinga JD, Martz S, Gil V, Wang XY, Jimenez M, Parsons S (2011) Two independent networks of interstitial cells of Cajal work cooperatively with the enteric nervous system to create colonic motor patterns. Front Neurosci 5:93. doi:10.3389/fnins.2011.00093

    Article  PubMed  Google Scholar 

  27. Huizinga JD, Thuneberg L, Kluppel M, Malysz J, Mikkelsen HB, Bernstein A (1995) W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature 373:347–349

    Article  PubMed  CAS  Google Scholar 

  28. Ibba Manneschi L, Pacini S, Corsani L, Bechi P, Faussone-Pellegrini MS (2004) Interstitital cells of Cajal in the human stomach: distribution and relationship with enteric innervation. Histol Histopathol 19:1153–1164

    PubMed  CAS  Google Scholar 

  29. Isozaki K, Hirota S, Miyagawa J, Taniguchi M, Shinomura Y, Matsuzawa Y (1997) Deficiency of c-kit+ cells in patients with a myopathic form of chronic idiopathic intestinal pseudo-obstruction. Am J Gastroenterol 92:332–334

    PubMed  CAS  Google Scholar 

  30. Isozaki K, Hirota S, Nakama A, Miyagawa J, Shinomura Y, Xu Z, Nomura S, Kitamura Y (1995) Disturbed intestinal movement, bile reflux to the stomach, and deficiency of c-kit-expressing cells in Ws/Ws mutant rats. Gastroenterology 109:456–464

    Article  PubMed  CAS  Google Scholar 

  31. Izbeki F, Asuzu DT, Lorincz A, Bardsley MR, Popko LN, Choi KM, Young DL, Hayashi Y, Linden DR, Kuro-o M, Farrugia G, Ordog T (2010) Loss of Kitlow progenitors, reduced stem cell factor and high oxidative stress underlie gastric dysfunction in progeric mice. J Physiol 588:3101–3117

    Article  PubMed  CAS  Google Scholar 

  32. Kashyap P, Gomez-Pinilla PJ, Pozo MJ, Cima RR, Dozois EJ, Larson DW, Ordog T, Gibbons SJ, Farrugia G (2011) Immunoreactivity for Ano1 detects depletion of Kit-positive interstitial cells of Cajal in patients with slow transit constipation. Neurogastroenterol Motil 23:760–765

    Article  PubMed  CAS  Google Scholar 

  33. Kashyap PC, Choi KM, Dutta N, Linden DR, Szurszewski JH, Gibbons SJ, Farrugia G (2010) Carbon monoxide reverses diabetic gastroparesis in NOD mice. Am J Physiol Gastrointest Liver Physiol 298:G1013–G1019. doi:10.1152/ajpgi.00069.2010

    Article  PubMed  CAS  Google Scholar 

  34. Kelly KA, Code CF, Elveback LR (1969) Patterns of canine gastric electrical activity. Am J Physiol 217:461–470

    PubMed  CAS  Google Scholar 

  35. Knowles CH, De Giorgio R, Kapur RP, Bruder E, Farrugia G, Geboes K, Lindberg G, Martin JE, Meier-Ruge WA, Milla PJ, Smith VV, Vandervinden JM, Veress B, Wedel T (2010) The London Classification of gastrointestinal neuromuscular pathology: report on behalf of the Gastro 2009 International Working Group. Gut 59:882–887

    Article  PubMed  Google Scholar 

  36. Komuro T, Seki K, Horiguchi K (1999) Ultrastructural characterization of the interstitial cells of Cajal. Arch Histol Cytol 62:295–316

    Article  PubMed  CAS  Google Scholar 

  37. Kurahashi M, Zheng H, Dwyer L, Ward SM, Don Koh S, Sanders KM (2011) A functional role for the ‘fibroblast-like cells’ in gastrointestinal smooth muscles. J Physiol 589:697–710

    Article  PubMed  CAS  Google Scholar 

  38. Lammers WJ, Ver Donck L, Stephen B, Smets D, Schuurkes JA (2009) Origin and propagation of the slow wave in the canine stomach: the outlines of a gastric conduction system. Am J Physiol Gastrointest Liver Physiol 296:G1200–G1210

    Article  PubMed  CAS  Google Scholar 

  39. Lang RJ, Zoltkowski BZ, Hammer JM, Meeker WF, Wendt I (2007) Electrical characterization of interstitial cells of Cajal-like cells and smooth muscle cells isolated from the mouse ureteropelvic junction. J Urol 177:1573–1580

    Article  PubMed  CAS  Google Scholar 

  40. Lee HT, Hennig GW, Fleming NW, Keef KD, Spencer NJ, Ward SM, Sanders KM, Smith TK (2007) Septal interstitial cells of Cajal conduct pacemaker activity to excite muscle bundles in human jejunum. Gastroenterology 133:907–917

    Article  PubMed  Google Scholar 

  41. Lin Z, Gao N, Hu HZ, Liu S, Gao C, Kim G, Ren J, Xia Y, Peck OC, Wood JD (2002) Immunoreactivity of Hu proteins facilitates identification of myenteric neurones in guinea-pig small intestine. Neurogastroenterol Motil 14:197–204

    Article  PubMed  CAS  Google Scholar 

  42. Lorincz A, Redelman D, Horvath VJ, Bardsley MR, Chen H, Ordog T (2008) Progenitors of interstitial cells of Cajal in the postnatal murine stomach. Gastroenterology 134:1083–1093

    Article  PubMed  Google Scholar 

  43. Lyford GL, He CL, Soffer E, Hull TL, Strong SA, Senagore AJ, Burgart LJ, Young-Fadok T, Szurszewski JH, Farrugia G (2002) Pan-colonic decrease in interstitial cells of Cajal in patients with slow transit constipation. Gut 51:496–501

    Article  PubMed  CAS  Google Scholar 

  44. Maeda H, Yamagata A, Nishikawa S, Yoshinaga K, Kobayashi S, Nishi K (1992) Requirement of c-kit for development of intestinal pacemaker system. Development 116:369–375

    PubMed  CAS  Google Scholar 

  45. McCloskey KD (2011) Interstitial cells of Cajal in the urinary tract. Handb Exp Pharmacol 202:233–254

    Google Scholar 

  46. Miller SM, Narasimhan RA, Schmalz PF, Soffer EE, Walsh RM, Krishnamurthi V, Pasricha PJ, Szurszewski JH, Farrugia G (2008) Distribution of interstitial cells of Cajal and nitrergic neurons in normal and diabetic human appendix. Neurogastroenterol Motil 20:349–357

    Article  PubMed  CAS  Google Scholar 

  47. O’Grady G, Du P, Cheng LK, Egbuji JU, Lammers WJ, Windsor JA, Pullan AJ (2010) Origin and propagation of human gastric slow-wave activity defined by high-resolution mapping. Am J Physiol. Gastrointest Liver Physiol 299:G585–G592. doi:10.1152/ajpgi.00125.2010

    Article  Google Scholar 

  48. Ordog T, Takayama I, Cheung WK, Ward SM, Sanders KM (2000) Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis. Diabetes 49:1731–1739

    Article  PubMed  CAS  Google Scholar 

  49. Rajan E, Gostout CJ, Lurken MS, Talley NJ, Locke GR, Szarka LA, Sumiyama K, Bakken TA, Stoltz GJ, Knipschield MA, Farrugia G (2008) Endoscopic “no hole” full-thickness biopsy of the stomach to detect myenteric ganglia. Gastrointest Endosc 68:301–307

    Article  PubMed  Google Scholar 

  50. Ramon Y Cajal S (1911) Histologie du systéme nerveux de l’Homme et des Vertébrés. Maloine Paris

    Google Scholar 

  51. Rhee PL, Lee JY, Son HJ, Kim JJ, Rhee JC, Kim S, Koh SD, Hwang SJ, Sanders KM, Ward SM (2011) Analysis of pacemaker activity in the human stomach. J Physiol. doi:10.1113/jphysiol.2011.217497

    Google Scholar 

  52. Rich A, Leddon SA, Hess SL, Gibbons SJ, Miller S, Xu X, Farrugia G (2007) Kit-like immunoreactivity in the zebrafish gastrointestinal tract reveals putative ICC. Dev Dyn 236:903–911

    Article  PubMed  CAS  Google Scholar 

  53. Richter A, Wit C, Vanderwinden JM, Wit J, Barthlen W (2009) Interstitial cells of Cajal in the vermiform appendix in childhood. Eur J Pediatr Surg 19:30–33

    Article  PubMed  CAS  Google Scholar 

  54. Rubin BP, Antonescu CR, Scott-Browne JP, Comstock ML, Gu Y, Tanas MR, Ware CB, Woodell J (2005) A knock-in mouse model of gastrointestinal stromal tumor harboring kit K641E. Cancer Res 65:6631–6639

    Article  PubMed  CAS  Google Scholar 

  55. Rumessen JJ, Vanderwinden JM (2003) Interstitial cells in the musculature of the gastrointestinal tract: Cajal and beyond. Int Rev Cytol 229:115–208

    Article  PubMed  CAS  Google Scholar 

  56. Sagstetter AM, Camp JJ, Lurken MS, Szurszewski JH, Farrugia G, Gibbons SJ, Robb RA (2007) Computer-aided classification of cell nuclei in the gastrointestinal tract by volume and principal axis. Proc SPIE 6514:1–9

    Google Scholar 

  57. Sha L, Farrugia G, Harmsen WS, Szurszewski JH (2007) Membrane potential gradient is carbon monoxide-dependent in mouse and human small intestine. Am J Physiol Gastrointest Liver Physiol 293:G438–G445. doi:10.1152/ajpgi.00037.2007

    Article  PubMed  CAS  Google Scholar 

  58. Sha L, Ou LL, Miller SM, Ma R, Szurszewski JH (1996) Cat pancreatic neurons: morphology, electrophysiological properties, and responses to 5-HT. Pancreas 13:111–124

    Article  PubMed  CAS  Google Scholar 

  59. Song G, Hirst GDS, Sanders KM, Ward SM (2005) Regional variation in ICC distribution, pacemaking activity and neural responses in the longitudinal muscle of the murine stomach. J Physiol 564:523–540

    Article  PubMed  CAS  Google Scholar 

  60. Strebelle S, Journel A (2001) Reservoir modeling using multiple-point statistics. SPE Annual Technical Conference and Exhibition 71324:1–11

    Google Scholar 

  61. 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:G1111–G1121

    PubMed  CAS  Google Scholar 

  62. Szurszewski JH (ed) (1987) Electrical basis of gastrointestinal motility. Raven, New York

    Google Scholar 

  63. Tharayil VS, Wouters MM, Stanich JE, Roeder JL, Lei S, Beyder A, Gomez-Pinilla PJ, Gershon MD, Maroteaux L, Gibbons SJ, Farrugia G (2010) Lack of serotonin 5-HT2B receptor alters proliferation and network volume of interstitial cells of Cajal in vivo. Neurogastroenterol Motil 22:462–469, e109–410. doi:10.1111/j.1365-2982.2009.01435.x

    Google Scholar 

  64. Thomsen L, Robinson TL, Lee JC, Farraway LA, Hughes MJ, Andrews DW, Huizinga JD (1998) Interstitial cells of Cajal generate a rhythmic pacemaker current. Nat Med 4:848–851

    Article  PubMed  CAS  Google Scholar 

  65. Torihashi S, Yokoi K, Nagaya H, Aoki K, Fujimoto T (2004) New monoclonal antibody (AIC) identifies interstitial cells of Cajal in the musculature of the mouse gastrointestinal tract. Auton Neurosci-Basic Clin 113:16–23

    Article  CAS  Google Scholar 

  66. Vanderwinden JM, Rumessen JJ, De Laet MH, Vanderhaeghen JJ, Schiffmann SN (1999) CD34 + cells in human intestine are fibroblasts adjacent to, but distinct from, interstitial cells of Cajal. Lab Invest 79:59–65

    PubMed  CAS  Google Scholar 

  67. Visser TD, Oud JL, Brakenhoff GJ (1992) Refractive index and axial distance measurements in 3-D microscopy. Optik 90:17–19

    Google Scholar 

  68. Ward SM, Burns AJ, Torihashi S, Harney SC, Sanders KM (1995) Impaired development of interstitial cells and intestinal electrical rhythmicity in steel mutants. Am J Physiol 269:C1577–C1585

    PubMed  CAS  Google Scholar 

  69. Ward SM, Burns AJ, Torihashi S, Sanders KM (1994) Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol 480:91–97

    PubMed  CAS  Google Scholar 

  70. Watkins CC, Sawa A, Blackshaw S, Barow RK, Snyder SH, Ferris CD (2000) Insulin restores neuronal nitric oxide synthase expression and function that is lost in diabetic gastropathy. J Clin Invest 106:373–384

    Article  PubMed  CAS  Google Scholar 

  71. Wedel T, Spiegler J, Soellner S, Roblick UJ, Schiedeck TH, Bruch HP, Krammer HJ (2002) Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon. Gastroenterology 123:1459–1467

    Article  PubMed  Google Scholar 

  72. Won KJ, Sanders KM, Ward SM (2005) Interstitial cells of Cajal mediate mechanosensitive responses in the stomach. Proc Natl Acad Sci USA 102:14913–14918

    Article  PubMed  CAS  Google Scholar 

  73. Wouters MM, Gibbons SJ, Roeder JL, Distad M, Ou Y, Strege PR, Szurszewski JH, Farrugia G (2007) Exogenous serotonin regulates proliferation of interstitial cells of Cajal in mouse jejunum through 5-HT2B receptors. Gastroenterology 133:897–906. doi:10.1053/j.gastro.2007.06.017

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We wish to thank the members of the Enteric Neuroscience Program, especially Dr Joseph Szurszewski and Mrs Kristy Zodrow, and members of the Gastrointestinal Research Group at the Auckland Bioengineering Institute for their support and assistance with this work. We are especially grateful to Dr Andrew Pullan for his leadership in establishing and maintaining the collaboration that is a key component in the studies described here. Thanks Andrew. These studies were supported by the following NIH Grants R01 DK57061 (GF, SJG), P01 DK 68055–P1 (GF, SJG), P01 DK 68055–B (SJG), R01 DK 52766 (GF, SJG), 1P30DK084567 (GF, SJG). Jerry Gao is supported by the University of Auckland Health Research Doctoral Scholarship, the Freemasons Postgraduate Scholarship and the R. H. T. Bates Postgraduate Scholarship.

Author information

Authors and Affiliations

  1. Enteric Neurosciences Program, Department Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Guggenheim 838, 200 First Street SW, Rochester, MN, 55905, USA

    Simon J. Gibbons & Gianrico Farrugia

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

    Jerry Gao

Authors
  1. Simon J. Gibbons
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jerry Gao
    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 Simon J. Gibbons .

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

Gibbons, S.J., Gao, J., Farrugia, G. (2013). ICC Network Density: Regulation and Consequences. 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_3

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-6561-0_3

  • 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