Annals of Biomedical Engineering

, Volume 38, Issue 9, pp 3022–3030 | Cite as

A Model of Slow Wave Propagation and Entrainment Along the Stomach

  • Martin L. Buist
  • Alberto Corrias
  • Yong Cheng Poh


Interstitial cells of Cajal (ICC) isolated from different regions of the stomach generate spontaneous electrical slow wave activity at different frequencies, with cells from the proximal stomach pacing faster than their distal counterparts. However, in vivo there exists a uniform pacing frequency; slow waves propagate aborally from the proximal stomach and subsequently entrain distal tissues. Significant resting membrane potential (RMP) gradients also exist within the stomach whereby membrane polarization generally increases from the fundus to the antrum. Both of these factors play a major role in the macroscopic electrical behavior of the stomach and as such, any tissue or organ level model of gastric electrophysiology should ensure that these phenomena are properly described. This study details a dual-cable model of gastric electrical activity that incorporates biophysically detailed single-cell models of the two predominant cell types, the ICC and smooth muscle cells. Mechanisms for the entrainment of the intrinsic pacing frequency gradient and for the establishment of the RMP gradient are presented. The resulting construct is able to reproduce experimentally recorded slow wave activity and provides a platform on which our understanding of gastric electrical activity can advance.


Smooth muscle cell Interstitial cell of Cajal Electrophysiology Resting membrane potential Carbon monoxide 



Resting membrane potential


Interstitial cells of Cajal


Smooth muscle cell


ICC from the myenteric plexus


Intramuscular ICC


  1. 1.
    Aliev, R. R., W. Richards, and J. P. Wikswo. A simple nonlinear model of electrical activity in the intestine. J. Theor. Biol. 204:21–28, 2000.CrossRefPubMedGoogle Scholar
  2. 2.
    Bayguinov, O., S. M. Ward, J. L. Kenyon, and K. M. Sanders. Voltage-gated Ca2+ currents are necessary for slow-wave propagation in the canine gastric antrum. Am. J. Physiol. Cell Physiol. 293:C1645–C1659, 2007.CrossRefPubMedGoogle Scholar
  3. 3.
    Bédard, C., and A. Destexhe. A modified cable formalism for modeling neuronal membranes at high frequencies. Biophys. J. 94:1133–1143, 2008.CrossRefPubMedGoogle Scholar
  4. 4.
    Bondarenko, V. E., and R. L. Rasmusson. Simulations of propagated mouse ventricular action potentials: effects of molecular heterogeneity. Am. J. Physiol. Heart Circ. Physiol. 293:H1816–H1832, 2007.CrossRefPubMedGoogle Scholar
  5. 5.
    Breitwieser, G. E. Mechanisms of K+ channel regulation. J. Membr. Biol. 152:1–11, 1996.CrossRefPubMedGoogle Scholar
  6. 6.
    Corrias, A., and M. L. Buist. A quantitative model of gastric smooth muscle cellular activation. Ann. Biomed. Eng. 35:1595–1607, 2007.CrossRefPubMedGoogle Scholar
  7. 7.
    Corrias, A., and M. L. Buist. Quantitative cellular description of gastric slow wave activity. Am. J. Physiol. Gastrointest. Liver Physiol. 294:G989–G995, 2008.CrossRefPubMedGoogle Scholar
  8. 8.
    Du, P., G. O’Grady, J. U. Egbuji, W. J. Lammers, D. Budgett, P. Nielsen, J. A. Windsor, A. J. Pullan, and L. K. Cheng. High-resolution mapping of in vivo gastrointestinal slow wave activity using flexible printed circuit board electrodes: methodology and validation. Ann. Biomed. Eng. 37:839–846, 2009.CrossRefPubMedGoogle Scholar
  9. 9.
    Durante, W., F. K. Johnson, and R. A. Johnson. Role of carbon monoxide in cardiovascular function. J. Cell. Mol. Med. 10:672–686, 2006.CrossRefPubMedGoogle Scholar
  10. 10.
    Edwards, F. R., and G. D. S. Hirst. An electrical description of the generation of slow waves in the antrum of the guinea-pig. J. Physiol. 564:213–232, 2005.CrossRefPubMedGoogle Scholar
  11. 11.
    Farrugia, G., W. A. Irons, J. L. Rae, M. G. Sarr, and J. H. Szurszewski. Activation of whole cell currents in isolated human jejunal circular smooth muscle cells by carbon monoxide. Am. J. Physiol. 264:G1184–G1189, 1993.PubMedGoogle Scholar
  12. 12.
    Farrugia, G., S. Lei, X. Lin, S. M. Miller, K. A. Nath, C. D. Ferris, M. Levitt, and J. H. Szurszewski. A major role for carbon monoxide as an endogenous hyperpolarizing factor in the gastrointestinal tract. Proc. Natl Acad. Sci. USA 100:8567–8570, 2003CrossRefPubMedGoogle Scholar
  13. 13.
    Farrugia, G., S. M. Miller, A. Rich, X. Liu, M. D. Maines, J. L. Rae, and J. H. Szurszewski. Distribution of heme oxygenase and effects of exogenous carbon monoxide in canine jejunum. Am. J. Physiol. 274:G350–G358, 1998.PubMedGoogle Scholar
  14. 14.
    Hashitani, H., A. P. Garcia-Londoño, G. D. S. Hirst, and F. R. Edwards. Atypical slow waves generated in gastric corpus provide dominant pacemaker activity in guinea pig stomach. J. Physiol. 569:459–465, 2005.CrossRefPubMedGoogle Scholar
  15. 15.
    Hirst, G. D. S., E. A. H. Beckett, K. M. Sanders, and S. M. Ward. Regional variation in contribution of myenteric and intramuscular interstitial cells of Cajal to generation of slow waves in mouse gastric antrum. J. Physiol. 540:1003–1012, 2002.CrossRefPubMedGoogle Scholar
  16. 16.
    Hirst, G. D. S., and F. R. Edwards. Electrical events underlying organized myogenic contractions of the guinea pig stomach. J. Physiol. 576:659–665, 2006.CrossRefPubMedGoogle Scholar
  17. 17.
    Huang, C. L., and L. D. Peachey. A reconstruction of charge movement during the action potential in frog skeletal muscle. Biophys. J. 61:1133–1146, 1992.CrossRefPubMedGoogle Scholar
  18. 18.
    Kadinov, B., D. Itzev, H. Gagov, T. Christova, T. B. Bolton, and D. Duridanova. Induction of heme oxygenase in guinea-pig stomach: roles in contraction and in single muscle cell ionic currents. Acta Physiol. Scand. 175:297–313, 2002.CrossRefPubMedGoogle Scholar
  19. 19.
    Kim, T. W., S. D. Koh, T. Ordög, S. M. Ward, and K. M. Sanders. Muscarinic regulation of pacemaker frequency in murine gastric interstitial cells of Cajal. J. Physiol. 546:415–425, 2003.CrossRefPubMedGoogle Scholar
  20. 20.
    Komuro, T. Structure and organization of interstitial cells of Cajal in the gastrointestinal tract. J. Physiol. 576:653–658, 2006.CrossRefPubMedGoogle Scholar
  21. 21.
    Lammers, W. J., B. Stephen, E. Adeghate, S. Ponery, and O. Pozzan. The slow wave does not propagate across the gastroduodenal junction in the isolated feline preparation. Neurogastroenterol. Motil. 10:339–349, 1998.CrossRefPubMedGoogle Scholar
  22. 22.
    Lammers, W. J. E. P., L. Ver Donck, B. Stephen, D. Smets, and J. A. J. Schuurkes. 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, 2009.CrossRefPubMedGoogle Scholar
  23. 23.
    Lee, H. T., G. W. Hennig, N. W. Fleming, K. D. Keef, N. J. Spencer, S. M. Ward, K. M. Sanders, and T. K. Smith. The mechanism and spread of pacemaker activity through myenteric interstitial cells of Cajal in human small intestine. Gastroenterology 132:1852–1865, 2007.CrossRefPubMedGoogle Scholar
  24. 24.
    Lin, A. S. H., M. L. Buist, N. P. Smith, and A. J. Pullan. Modelling slow wave activity in the small intestine. J. Theor. Biol. 242:356–362, 2006.CrossRefPubMedGoogle Scholar
  25. 25.
    Malysz, J., G. Donnelly, and J. D. Huizinga. Regulation of slow wave frequency by IP(3)-sensitive calcium release in the murine small intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 280:G439–G448, 2001.PubMedGoogle Scholar
  26. 26.
    Pullan, A., L. Cheng, R. Yassi, and M. Buist. Modelling gastrointestinal bioelectric activity. Prog. Biophys. Mol. Biol. 85:523–550, 2004.CrossRefPubMedGoogle Scholar
  27. 27.
    Sanders, K. M., S. D. Koh, and S. M. Ward. Interstitial cells of cajal as pacemakers in the gastrointestinal tract. Annu. Rev. Physiol. 68:307–343, 2006.CrossRefPubMedGoogle Scholar
  28. 28.
    Spitzer, V., M. J. Ackerman, A. L. Scherzinger, and D. Whitlock. The visible human male: a technical report. J. Am. Med. Inform. Assoc. 3:118–130, 1996.PubMedGoogle Scholar
  29. 29.
    Stratton, C. J., S. M. Ward, K. Horiguchi, and K. M. Sanders. Immunocytochemical identification of interstitial cells of Cajal in the murine fundus using a live-labelling technique. Neurogastroenterol. Motil. 19:152–159, 2007.CrossRefPubMedGoogle Scholar
  30. 30.
    Szurszewski, J. Electrical basis for gastrointestinal motility. In: Physiology of the Gastrointestinal Tract, edited by L. Johnson. New York: Raven Press, 1987, pp. 383–422.Google Scholar
  31. 31.
    Szurszewski, J. H., and G. Farrugia. Carbon monoxide is an endogenous hyperpolarizing factor in the gastrointestinal tract. Neurogastroenterol. Motil. 16(Suppl 1):81–85, 2004.CrossRefPubMedGoogle Scholar
  32. 32.
    Wang, R., and L. Wu. The chemical modification of KCa channels by carbon monoxide in vascular smooth muscle cells. J. Biol. Chem. 272:8222–8226, 1997.CrossRefPubMedGoogle Scholar
  33. 33.
    Ward, S. M., R. E. Dixon, A. de Faoite, and K. M. Sanders. Voltage-dependent calcium entry underlies propagation of slow waves in canine gastric antrum. J. Physiol. 561:793–810, 2004.CrossRefPubMedGoogle Scholar

Copyright information

© Biomedical Engineering Society 2010

Authors and Affiliations

  • Martin L. Buist
    • 1
  • Alberto Corrias
    • 1
  • Yong Cheng Poh
    • 1
  1. 1.Division of BioengineeringNational University of SingaporeSingaporeSingapore

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