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Chapter 4
Interstitial cells of Cajal in enteric neurotransmission
  1. S M Ward
  1. Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA
  1. Associate Professor S M Ward. sean{at}physio.unr.edu

https://doi.org/10.1136/gut.47.suppl_4.iv40

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    Specialised cells known as interstitial cells of Cajal (ICCs), distributed in specific locations within the tunica muscularis of the gastrointestinal tract, serve as electrical pacemakers and mediators of enteric neurotransmission. Until recently, evidence to support a functional role of these cells has been, for the most part, indirect.

    The role of ICCs in pacemaking or neurotransmission has been tested by experiments in which: (i) ICCs were removed by dissection1-3; (ii) ICCs were lesioned by cytotoxic chemicals thought to have specificity for these cells4-6; (iii) the excitability properties and responses to drugs were directly studied in isolated ICCs7 8; (iv) morphological studies revealed close relationships between ICCs and varicose nerve fibres (see fig 1); and (v) ICCs responded to neurotransmitters when studied using immunohistochemical techniques.9 10

    Figure 1

    Confocal micrographs of whole mount preparations showing double labelling with the receptor tyrosine kinase, Kit (FITC; A) and nitric oxide synthase (NOS; Texas Red; B) or vesicular acetylcholine transporter (vAChT) antibodies in the circular muscle layer of the murine gastric fundus. (A) Spindle shaped interstitial cells of circular and longitudinal muscle (IC-IM) immunopositive for Kit (green; arrows) within the circular muscle layer. (B) NOS-LI in enteric inhibitory nerves (arrows); IC-IM also appeared immunoreactive for NOS (C). (D, E) Double labelling of Kit (D) and vAChT (E). Double labelling of Kit-LI and vAChT-LI is shown in (F). Courtesy of Wang et al.30

    Recent findings have shown that several classes of ICCs of the mouse and other species express the receptor tyrosine kinase, Kit. Activation of Kit by its ligand, stem cell factor, or “steel” factor is important in the development of ICCs because blockade of Kit with neutralising antibodies11 12 or mutations inc-kit 13 14 orsteel 15 impair the development of ICCs at …

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    Footnotes

    • Abbreviations used in this paper:
      ICC
      interstitial cells of Cajal
      NOS
      nitric oxide synthase
      vAChT
      vesicular acetylcholine transporter
      IC-MY
      interstitial cells of the myenteric plexus
      IC-IM
      interstitial cells of circular and longitudinal muscle
      IC-DMP
      interstitial cells of deep muscular plexus
      cGMP
      cyclic guanosine monophosphate