Interstitial Cells of Cajal: Update on Basic and Clinical Science

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The basic science and clinical interest in the networks of interstitial cells of Cajal (ICC) keep growing, and here, research from 2010 to mid-2013 is highlighted. High-resolution gastrointestinal manometry and spatiotemporal mapping are bringing exciting new insights into motor patterns, their function and their myogenic and neurogenic origins, as well as the role of ICC. Critically important knowledge is emerging on the partaking of PDGFRα+ cells in ICC pacemaker networks. Evidence is emerging that ICC and PDGFRα+ cells have unique direct roles in muscle innervation. Chronic constipation is associated with loss and injury to ICC, which is stimulating extensive research into maintenance and repair of ICC after injury. In gastroparesis, high-resolution electrical and mechanical studies are beginning to elucidate the pathophysiological role of ICC and the pacemaker system in this condition. Receptors and ion channels that play a role in ICC function are being discovered and characterized, which paves the way for pharmacological interventions in gut motility disorders through ICC.

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Fig. 1
Fig. 2
Fig. 3



interstitial cells of Cajal


ICC associated with the myenteric plexus (also called ICC-MY and ICC-AP)


ICC associated with the deep muscular plexus (small intestine)


ICC associated with the submuscular plexus (colon)


Intramuscular ICC


tyrosine-protein kinase Kit or CD117




Enteric nervous system

PDGFRα+ cells:

Platelet-derived growth factor receptor-alpha positive cells (specialized fibroblast-like cells)


Long Distance Contraction (colon)


Rhythmic Propulsive Motor Complex (colon)


High Amplitude Propulsive Contraction (an RPMC identified in human colon with amplitude > 100 mm Hg)


5-hydroxy tryptamine


    Papers of particular interest, published recently, have been highlighted as: • Of importance, •• Of major importance

    1. 1.

      Li Z, Chalazonitis A, Huang YY, Mann JJ, Margolis KG, Yang QM, et al. Essential roles of enteric neuronal serotonin in gastrointestinal motility and the development/survival of enteric dopaminergic neurons. J Neurosci. 2011;31:8998–9009.

    2. 2.

      •• Groneberg D, Konig P, Lies B, Jager R, Seidler B, Klein S, et al. Cell-specific deletion of nitric oxide-sensitive guanylyl cyclase reveals a dual pathway for nitrergic neuromuscular transmission in the murine fundus. Gastroenterology. 2013. doi:10.1053/j.gastro.2013.03.042. This study is of critical importance. Therefore, it should be repeated by another lab, and the differences between direct muscle innervation and innervation via ICC should be further investigated.

    3. 3.

      Groneberg D, Konig P, Koesling D, Friebe A. Nitric oxide-sensitive guanylyl cyclase is dispensable for nitrergic signaling and gut motility in mouse intestinal smooth muscle. Gastroenterology. 2011;140:1608–17.

    4. 4.

      Sanders KM, Koh SD, Ro S, Ward SM. Regulation of gastrointestinal motility–insights from smooth muscle biology. Nat Rev Gastroenterol Hepatol. 2012;9:633–45.

    5. 5.

      Powley TL, Gilbert JM, Baronowsky EA, Billingsley CN, Martin FN, Phillips RJ. Vagal sensory innervation of the gastric sling muscle and antral wall: implications for gastro-esophageal reflux disease? Neurogastroenterol Motil. 2012;24:e526–37.

    6. 6.

      • Powley TL, Phillips RJ. Vagal intramuscular array afferents form complexes with interstitial cells of Cajal in gastrointestinal smooth muscle: analogues of muscle spindle organs? Neuroscience. 2011;186:188–200. Important insights into the role of ICC in mechano-sensory transduction.

    7. 7.

      Powley TL, Wang XY, Fox EA, Phillips RJ, Liu LW, Huizinga JD. Ultrastructural evidence for communication between intramuscular vagal mechanoreceptors and interstitial cells of Cajal in the rat fundus. Neurogastroenterol Motil. 2008;20:69–79.

    8. 8.

      Huizinga JD, Zarate N, Farrugia G. Physiology, injury, and recovery of interstitial cells of Cajal: basic and clinical science. Gastroenterology. 2009;137:1548–56.

    9. 9.

      Bernardini N, Segnani C, Ippolito C, De Giorgio R, Colucci R, Faussone-Pellegrini MS, et al. Immunohistochemical analysis of myenteric ganglia and interstitial cells of Cajal in ulcerative colitis. J Cell Mol Med. 2012;16:318–27.

    10. 10.

      Wang XY, Zarate N, Soderholm JD, Bourgeois JM, Liu LW, Huizinga JD. Ultrastructural injury to interstitial cells of Cajal and communication with mast cells in Crohn’s disease. Neurogastroenterol Motil. 2007;19:349–64.

    11. 11.

      Rumessen JJ, Vanderwinden JM, Horn T. Crohn’s disease: ultrastructure of interstitial cells in colonic myenteric plexus. Cell Tissue Res. 2011;344:471–9.

    12. 12.

      Rumessen JJ, Vanderwinden JM, Horn T. Crohn’s disease of the colon: ultrastructural changes in submuscular interstitial cells of Cajal. Cell Tissue Res. 2011;343:421–8.

    13. 13.

      Kashyap P, Gomez-Pinilla PJ, Pozo MJ, Cima RR, Dozois EJ, Larson DW, et al. Immunoreactivity for Ano1 detects depletion of Kit-positive interstitial cells of Cajal in patients with slow transit constipation. Neurogastroenterol Motil. 2011;23:760–5.

    14. 14.

      Bettolli M, De Carli C, Cornejo-Palma D, Jolin-Dahel K, Wang XY, Huizinga J, et al. Interstitial cell of Cajal loss correlates with the degree of inflammation in the human appendix and reverses after inflammation. J Pediatr Surg. 2012;47:1891–9.

    15. 15.

      Faussone-Pellegrini MS, Grover M, Pasricha PJ, Bernard CE, Lurken MS, Smyrk TC, et al. Ultrastructural differences between diabetic and idiopathic gastroparesis. J Cell Mol Med. 2012;16:1573–81.

    16. 16.

      •• Grover M, Bernard CE, Pasricha PJ, Lurken MS, Faussone-Pellegrini MS, Smyrk TC, et al. Clinical-histological associations in gastroparesis: results from the Gastroparesis Clinical Research Consortium. Neurogastroenterol Motil. 2012;24:531–9. e249. Multicenter study to find correlates in diabetic and idiopathic gastroparesis between ICC injury, inflammation, nerve injury, and function.

    17. 17.

      Grover M, Farrugia G, Lurken MS, Bernard CE, Faussone-Pellegrini MS, Smyrk TC, et al. Cellular changes in diabetic and idiopathic gastroparesis. Gastroenterology. 2011;140:1575–85.e8.

    18. 18.

      • O’Grady G, Angeli TR, Du P, Lahr C, Lammers WJ, Windsor JA, et al. Abnormal initiation and conduction of slow-wave activity in gastroparesis, defined by high-resolution electrical mapping. Gastroenterology. 2012;143:589–98.e1.. Important insights into abnormal electrical activity in the stomach of gastroparesis patients.

    19. 19.

      Kim ER, Kim KM, Lee JY, Joo M, Kim S, Noh JH, et al. The clue of Interstitial Cell of Cajalopathy (ICCpathy) in human diabetic gastropathy: the ultrastructural and electrical clues of ICCpathy in human diabetic gastropathy. Exp Toxicol Pathol. 2012;64:521–6.

    20. 20.

      Jabari S, AB da Silveira, EC de Oliveira, K Quint, A Wirries, W Neuhuber, A Brehmer. Interstitial cells of Cajal: crucial for the development of megacolon in human Chagas disease? Colorectal Dis 2013;15:592–8.

    21. 21.

      Adad SJ, Silva GB, Jammal AA. The significantly reduced number of interstitial cells of Cajal in chagasic megacolon (CM) patients might contribute to the pathophysiology of CM. Virchows Arch. 2012;461:385–92.

    22. 22.

      Gfroerer S, Metzger R, Fiegel H, Ramachandran P, Rolle U. Differential changes in intrinsic innervation and interstitial cells of Cajal in small bowel atresia in newborns. World J Gastroenterol. 2010;16:5716–21.

    23. 23.

      Tander B, Bicakci U, Sullu Y, Rizalar R, Ariturk E, Bernay F, et al. Alterations of Cajal cells in patients with small bowel atresia. J Pediatr Surg. 2010;45:724–8.

    24. 24.

      Jin QH, Shen HX, Wang H, Shou QY, Liu Q. Curcumin improves expression of SCF/c-kit through attenuating oxidative stress and NF-kappaB activation in gastric tissues of diabetic gastroparesis rats. Diabetol Metab Syndr. 2013;5:12.

    25. 25.

      Mogami S, H Suzuki, H Tsugawa, S Fukuhara, T Hibi. Impaired heme oxygenase-1 induction in the gastric antrum induces disruption of the interstitial cells of Cajal network in a rat model of streptozotocin-induced diabetes. Neurogastroenterol Motil 2013

    26. 26.

      Lammers WJ, HM Al-Bloushi, SA Al-Eisae, FA Al-Dhaheri, BS Stephen, R John, S Dhanasekaran, SM Karam. Slow wave propagation and ICC plasticity in the small intestine of diabetic rats. Exp Physiol 2011

    27. 27.

      Domenech A, Pasquinelli G, De Giorgio R, Gori A, Bosch F, Pumarola M, et al. Morphofunctional changes underlying intestinal dysmotility in diabetic RIP-I/hIFNbeta transgenic mice. Int J Exp Pathol. 2011;92:400–12.

    28. 28.

      Choi KM, Gibbons SJ, Nguyen TV, Stoltz GJ, Lurken MS, Ordog T, et al. Heme oxygenase-1 protects interstitial cells of Cajal from oxidative stress and reverses diabetic gastroparesis. Gastroenterology. 2008;135:2055–64. 2064 e1.

    29. 29.

      Huizinga JD. MS Faussone-Pellegrini About the presence of interstitial cells of Cajal outside the musculature of the gastrointestinal tract. J Cell Mol Med. 2005;9:468–73.

    30. 30.

      Faussone-Pellegrini MS, Cortesini C, Romagnoli P. The ultrastructure of the muscle coat of the human gasto-esophageal junction, with special reference to “interstitial cells of Cajal”. Front Auton Neurosci. 2013;7:49.

    31. 31.

      Huizinga JD, Chen JH, Mikkelsen HB, Wang XY, Parsons SP, Zhu YF. Interstitial cells of Cajal, from structure to function. Front Neurosci. 2013;7:43.

    32. 32.

      Wang XY, Paterson C, Huizinga JD. Cholinergic and nitrergic innervation of ICC-DMP and ICC-IM in the human small intestine. Neurogastroenterol Motil. 2003;15:531–43.

    33. 33.

      Shi LL, Liu MD, Chen M, Zou XP. Involvement of interstitial cells of Cajal in experimental severe acute pancreatitis in rats. World J Gastroenterol. 2013;19:2179–86.

    34. 34.

      Hoshino M, Omura N, Yano F, Tsuboi K, Kashiwagi H, Yanaga K. Immunohistochemical study of the muscularis externa of the esophagus in achalasia patients. Dis Esophagus. 2013;26:14–21.

    35. 35.

      Knowles CH, Farrugia G. Gastrointestinal neuromuscular pathology in chronic constipation. Best Pract Res Clin Gastroenterol. 2011;25:43–57.

    36. 36.

      Gomez-Pinilla PJ, Gibbons SJ, Sarr MG, Kendrick ML, Shen KR, Cima RR, et al. Changes in interstitial cells of cajal with age in the human stomach and colon. Neurogastroenterol Motil. 2011;23:36–44.

    37. 37.

      • Huizinga JD, Martz S, Gill V, Wang X-Y, Jimenez M, Parsons S. Two independent networks of interstitial cells of Cajal work cooperatively with the enteric nervous system to create colonic motor patterns. Front Neurosci. 2011;5(93):1–12. This study shows howTTX-sensitivityof a motor pattern does not exclude myogenic control.

    38. 38.

      • Costa M, KN Dodds, L Wiklendt, NJ Spencer, SJ Brookes, PG Dinning. Neurogenic and myogenic motor activity in the colon of the guinea-pig, mouse, rabbit and rat. Am J Physiol Gastrointest Liver Physiol. 2013;305:G749–59. Important evidence and discussion on neural versus myogenic control of colonic motility.

    39. 39.

      Arkwright JW, Dickson A, Maunder SA, Blenman NG, Lim J, O’Grady G, et al. The effect of luminal content and rate of occlusion on the interpretation of colonic manometry. Neurogastroenterol Motil. 2013;25:e52–9.

    40. 40.

      Dinning PG, Costa M, Brookes SJ, Spencer NJ. Neurogenic and myogenic motor patterns of rabbit proximal, mid, and distal colon. Am J Physiol Gastrointest Liver Physiol. 2012;303:G83–92.

    41. 41.

      Lentle RG, Janssen PW, Asvarujanon P, Chambers P, Stafford KJ, Hemar Y. High-definition spatiotemporal mapping of contractile activity in the isolated proximal colon of the rabbit. J Comp Physiol B. 2008;178:257–68.

    42. 42.

      • Dickson EJ, Heredia DJ, McCann CJ, Hennig GW, Smith TK. The mechanisms underlying the generation of the colonic migrating motor complex in both wild-type and nNOS knockout mice. Am J Physiol Gastrointest Liver Physiol. 2010;298:G222–32. Important study on neural control of colonic motility.

    43. 43.

      • Carbone SE, Dinning PG, Costa M, Spencer NJ, Brookes SJ, Wattchow DA. Ascending excitatory neural pathways modulate slow phasic myogenic contractions in the isolated human colon. Neurogastroenterol Motil. 2013;25:670–6. This paper gives important insights into the origins of phasic contractions in the human colon using in vitro techniques.

    44. 44.

      Davidson JB, O’Grady G, Arkwright JW, Zarate N, Scott SM, Pullan AJ, et al. Anatomical registration and three-dimensional visualization of low and high-resolution pan-colonic manometry recordings. Neurogastroenterol Motil. 2011;23:387–91.

    45. 45.

      • Chen JH, Zhang Q, Yu Y, Li K, Liao H, Jiang LS, et al. Neurogenic and myogenic properties of pan-colonic motor patterns and their spatiotemporal organization in rats. PLoS ONE. 2013;8:e60474. This paper provides insight into the myogenic and ICC-related components of TTX-sensitive and -insensitive motor patterns in the rat colon.

    46. 46.

      Pluja L, Alberti E, Fernandez E, Mikkelsen HB, Thuneberg L, Jimenez M. Evidence supporting presence of two pacemakers in rat colon. Am J Physiol Gastrointest Liver Physiol. 2001;281:G255–66.

    47. 47.

      Yoneda S, Fukui H, Takaki M. Pacemaker activity from submucosal interstitial cells of Cajal drives high-frequency and low-amplitude circular muscle contractions in the mouse proximal colon. Neurogastroenterol Motil. 2004;16:621–7.

    48. 48.

      Gil V, SP Parsons, D Gallego, JD Huizinga, M Jimenez. Effects of hydrogen sulphide on motility patterns in the rat colon. Br J Pharmacol 2013

    49. 49.

      Huizinga JD, Waterfall WE. Electrical correlate of circumferential contractions in human colonic circular muscle. Gut. 1988;29:10–6.

    50. 50.

      Spencer NJ, Kyloh M, Wattchow DA, Thomas A, Sia TC, Brookes SJ, et al. Characterization of motor patterns in isolated human colon: are there differences in patients with slow-transit constipation? Am J Physiol Gastrointest Liver Physiol. 2012;302:G34–43.

    51. 51.

      Singh S, Heady S, Coss-Adame E, Rao SS. Clinical utility of colonic manometry in slow transit constipation. Neurogastroenterol Motil. 2013;25:487–95.

    52. 52.

      Zhu YF, X-Y Wang, B-J Lowie, S Parsons, W E., W Kunze, A Pawelka, JD Huizinga Enteric sensory neurons communicate with interstitial cells of Cajal to affect pacemaker activity in the small intestine. Pflugers Arch 2013; In press.

    53. 53.

      Gabella G. Innervation of the gastrointestinal tract. Int Rev Cytol. 1979;59:129–93.

    54. 54.

      Kim TW, Koh SD, Ordog T, Ward SM, Sanders KM. Muscarinic regulation of pacemaker frequency in murine gastric interstitial cells of Cajal. J Physiol. 2003;546:415–25.

    55. 55.

      Ramon y Cajal S Histologie du systéme nerveux de l’ homme et des vertébrés. 1911 2

    56. 56.

      Burns AJ, Lomax AE, Torihashi S, Sanders KM, Ward SM. Interstitial cells of Cajal mediate inhibitory neurotransmission in the stomach. Proc Natl Acad Sci U S A. 1996;93:12008–13.

    57. 57.

      Ward SM, Beckett EA, Wang X, Baker F, Khoyi M, Sanders KM. Interstitial cells of Cajal mediate cholinergic neurotransmission from enteric motor neurons. J Neurosci. 2000;20:1393–403.

    58. 58.

      Huizinga JD, Liu LW, Fitzpatrick A, White E, Gill S, Wang XY, et al. Deficiency of intramuscular ICC increases fundic muscle excitability but does not impede nitrergic innervation. Am J Physiol Gastrointest Liver Physiol. 2008;294:G589–94.

    59. 59.

      Zhang RX, Wang XY, Chen D, Huizinga JD. Role of interstitial cells of Cajal in the generation and modulation of motor activity induced by cholinergic neurotransmission in the stomach. Neurogastroenterol Motil. 2011;23:e356–71.

    60. 60.

      Duffy AM, Cobine CA, Keef KD. Changes in neuromuscular transmission in the W/W(v) mouse internal anal sphincter. Neurogastroenterol Motil. 2012;24:e41–55.

    61. 61.

      • Klein S, Seidler B, Kettenberger A, Sibaev A, Rohn M, Feil R, et al. Interstitial cells of Cajal integrate excitatory and inhibitory neurotransmission with intestinal slow-wave activity. Nat Commun. 2013;4:1630. This paper contributes to our understanding of direct innervation to smooth muscle and innervation mediated by ICC using genetically modified mice.

    62. 62.

      Bhetwal BP, Sanders KM, An C, Trappanese DM, Moreland RS, Perrino BA. Ca2+ sensitization pathways accessed by cholinergic neurotransmission in the murine gastric fundus. J Physiol. 2013;591:2971–86.

    63. 63.

      Faussone-Pellegrini MS, Gay J, Vannucchi MG, Corsani L, Fioramonti J. Alterations of neurokinin receptors and interstitial cells of Cajal during and after jejunal inflammation induced by Nippostrongylus brasiliensis in the rat. Neurogastroenterol Motil. 2002;14:83–95.

    64. 64.

      Wang XY, Vannucchi MG, Nieuwmeyer F, Ye J, Faussone-Pellegrini MS, Huizinga JD. Changes in interstitial cells of Cajal at the deep muscular plexus are associated with loss of distention-induced burst-type muscle activity in mice infected by Trichinella spiralis. Am J Pathol. 2005;167:437–53.

    65. 65.

      Wang XY, Berezin I, Mikkelsen HB, Der T, Bercik P, Collins SM, et al. Pathology of interstitial cells of Cajal in relation to inflammation revealed by ultrastructure but not immunohistochemistry. Am J Pathol. 2002;160:1529–40.

    66. 66.

      Pokkunuri V, Pimentel M, Morales W, Jee SR, Alpern J, Weitsman S, et al. Role of cytolethal distending toxin in altered stool form and bowel phenotypes in a rat model of post-infectious irritable bowel syndrome. J Neurogastroenterol Motil. 2012;18:434–42.

    67. 67.

      Lorincz A, Redelman D, Horvath VJ, Bardsley MR, Chen H, Ordog T. Progenitors of interstitial cells of cajal in the postnatal murine stomach. Gastroenterology. 2008;134:1083–93.

    68. 68.

      Stanich JE, Gibbons SJ, Eisenman ST, Bardsley MR, Rock JR, Harfe BD, et al. Ano1 as a regulator of proliferation. Am J Physiol Gastrointest Liver Physiol. 2011;301:G1044–51.

    69. 69.

      Mazzone A, Eisenman ST, Strege PR, Yao Z, Ordog T, Gibbons SJ, et al. Inhibition of cell proliferation by a selective inhibitor of the Ca(2+)-activated Cl(-) channel, Ano1. Biochem Biophys Res Commun. 2012;427:248–53.

    70. 70.

      Ordog T, Syed SA, Hayashi Y, Asuzu DT. Epigenetics and chromatin dynamics: a review and a paradigm for functional disorders. Neurogastroenterol Motil. 2012;24:1054–68.

    71. 71.

      Camilleri M, Grover M, Farrugia G. What are the important subsets of gastroparesis? Neurogastroenterol Motil. 2012;24:597–603.

    72. 72.

      • Grover M, Bernard CE, Pasricha PJ, Parkman HP, Abell TL, Nguyen LA, et al. Platelet-derived growth factor receptor alpha (PDGFRalpha)-expressing “fibroblast-like cells” in diabetic and idiopathic gastroparesis of humans. Neurogastroenterol Motil. 2012;24:844–52. Important information on PDGFRα+ positive cells in the human gastroparesis.

    73. 73.

      O’Grady G, Du P, Paskaranandavadivel N, Angeli TR, Lammers WJ, Asirvatham SJ, et al. Rapid high-amplitude circumferential slow wave propagation during normal gastric pacemaking and dysrhythmias. Neurogastroenterol Motil. 2012;24:e299–312.

    74. 74.

      Lowie BJ, Wang XY, White EJ, Huizinga JD. On the origin of rhythmic calcium transients in the ICC-MP of the mouse small intestine. Am J Physiol Gastrointest Liver Physiol. 2011;301:G835–45.

    75. 75.

      Lee J, Kim YD, Park CG, Kim MY, Chang IY, Zuo DC, et al. Neurotensin modulates pacemaker activity in interstitial cells of Cajal from the mouse small intestine. Mol Cells. 2012;33:509–16.

    76. 76.

      Park CG, Kim YD, Kim MY, Koh JW, Jun JY, Yeum CH, et al. Effects of prostaglandin F2 alpha on small intestinal interstitial cells of Cajal. World J Gastroenterol. 2011;17:1143–51.

    77. 77.

      Liu HN, Ohya S, Nishizawa Y, Sawamura K, Iino S, Syed MM, et al. Serotonin augments gut pacemaker activity via 5-HT3 receptors. PLoS One. 2011;6:e24928.

    78. 78.

      Si X, Huang L, Gong Y, Lu J, Lin L. Role of calcium in activation of hyperpolarization-activated cyclic nucleotide-gated channels caused by cholecystokinin octapeptide in interstitial cells of cajal. Digestion. 2012;85:266–75.

    79. 79.

      Gong YY, Si XM, Lin L, Lu J. Mechanisms of cholecystokinin-induced calcium mobilization in gastric antral interstitial cells of Cajal. World J Gastroenterol. 2012;18:7184–93.

    80. 80.

      Lee JH, Kim SY, Kwon YK, Kim BJ, So I. Characteristics of the cholecystokinin-induced depolarization of pacemaking activity in cultured interstitial cells of cajal from murine small intestine. Cell Physiol Biochem. 2013;31:542–54.

    81. 81.

      Kim YD, Han KT, Lee J, Park CG, Kim MY, Shahi PK, et al. Effects of sphingosine-1-phosphate on pacemaker activity of interstitial cells of Cajal from mouse small intestine. Mol Cells. 2013;35:79–86.

    82. 82.

      Kim BJ, Kwon YK, Kim E, So I. Effects of histamine on cultured interstitial cells of cajal in murine small intestine. Korean J Physiol Pharmacol. 2013;17:149–56.

    83. 83.

      Kim BJ, Chang IY, Choi S, Jun JY, Jeon JH, Xu WX, et al. Involvement of Na(+)-leak channel in substance P-induced depolarization of pacemaking activity in interstitial cells of Cajal. Cell Physiol Biochem. 2012;29:501–10.

    84. 84.

      Wright GW, Parsons SP, Huizinga JD. Ca(2+) sensitivity of the maxi chloride channel in interstitial cells of Cajal. Neurogastroenterol Motil. 2012;24:e221–34.

    85. 85.

      Hwang SJ, Blair PJ, Britton FC, O’Driscoll KE, Hennig G, Bayguinov YR, et al. Expression of anoctamin 1/TMEM16A by interstitial cells of Cajal is fundamental for slow wave activity in gastrointestinal muscles. J Physiol. 2009;587:4887–904.

    86. 86.

      Gomez-Pinilla PJ, Gibbons SJ, Bardsley MR, Lorincz A, Pozo MJ, Pasricha PJ, et al. Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol. 2009;296:G1370–81.

    87. 87.

      Parsons SP, JD Huizinga. Gating of maxi channels observed from pseudo phase portraits. Am J Physiol Cell Physiol 2013

    88. 88.

      Parsons SP, Kunze WA, Huizinga JD. Maxi-channels recorded in situ from ICC and pericytes associated with the mouse myenteric plexus. Am J Physiol Cell Physiol. 2012;302:C1055–69.

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    The study was financially supported by Grant 81170249 from the National Natural Science Foundation of China (NSFC) and by Grant MOP12874 from the Canadian Institutes of Health Research (CIHR). As always, we appreciate the discussions with Dr. Xuan-Yu Wang.

    Compliance with Ethics Guidelines

    Conflict of Interest

    Dr. Huizinga states that this work was possible due to ongoing research support from the Canadian Institutes of Health Research (CIHR). Dr. Chen declares that this work was possible due to ongoing research support from the National Natural Science Foundation of China (NSFC).

    Human and Animal Rights and Informed Consent

    This article does not contain any studies with human or animal subjects performed by the authors.

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    Correspondence to Jan D. Huizinga.

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    This article is part of the Topical Collection on Neuromuscular Disorders of the Gastrointestinal Tract

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    Huizinga, J.D., Chen, J. Interstitial Cells of Cajal: Update on Basic and Clinical Science. Curr Gastroenterol Rep 16, 363 (2014) doi:10.1007/s11894-013-0363-z

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    • Interstitial cells of Cajal (ICC)
    • PDGFRα+
    • Enteric nervous system (ENS)
    • Chronic constipation
    • Gastroparesis
    • Inflammation
    • Colon motility
    • Pacemaker cells
    • Nitric oxide
    • Guanylate cyclase
    • Gastroparesis
    • Chronic constipation
    • Gut transit
    • Gastrointestinal transit
    • Ion channels
    • Receptors