Skip to main content
Log in

Problems with extracellular recording of electrical activity in gastrointestinal muscle

  • Opinion
  • Published:

From Nature Reviews Gastroenterology & Hepatology

View current issue Sign up to alerts

Abstract

Motility patterns of the gastrointestinal tract are important for efficient processing of nutrients and waste. Peristalsis and segmentation are based on rhythmic electrical slow waves that generate the phasic contractions fundamental to gastrointestinal motility. Slow waves are generated and propagated actively by interstitial cells of Cajal (ICC), and these events conduct to smooth muscle cells to elicit excitation–contraction coupling. Extracellular electrical recording has been utilized to characterize slow-wave generation and propagation and abnormalities that might be responsible for gastrointestinal motility disorders. Electrode array recording and digital processing are being used to generate data for models of electrical propagation in normal and pathophysiological conditions. Here, we discuss techniques of extracellular recording as applied to gastrointestinal organs and how mechanical artefacts might contaminate these recordings and confound their interpretation. Without rigorous controls for movement, current interpretations of extracellular recordings might ascribe inaccurate behaviours and electrical anomalies to ICC networks and gastrointestinal muscles, bringing into question the findings and validity of models of gastrointestinal electrophysiology developed from these recordings.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1: Schematic representations of electrophysiological recording techniques.
Figure 2: Morphological considerations in gastrointestinal muscles.
Figure 3: Stabilization of movement abolishes biopotentials in human gastric muscles despite the persistence of electrical slow waves.
Figure 4: Comparison of action potentials recorded simultaneously from mouse heart with intracellular and extracellular electrocardiogram electrodes.
Figure 5: Effects of different filtering parameters on slow waves recorded directly from interstitial cells of Cajal.

Similar content being viewed by others

References

  1. Alvarez, W. C. & Mahoney, L. J. Action currents in stomach and intestine. Am. J. Physiol. 58, 476–493 (1922).

    Article  CAS  Google Scholar 

  2. Richter, C. P. Action currents from the stomach. Am. J. Physiol. 67, 612–633 (1924).

    Article  Google Scholar 

  3. Janse, M. J. & Rosen, M. R. History of arrhythmias. Handb. Exp. Pharmacol. 171, 1–39 (2006).

    Article  Google Scholar 

  4. O'Grady, G. et al. Abnormal initiation and conduction of slow-wave activity in gastroparesis, defined by high-resolution electrical mapping. Gastroenterology 143, 589–598 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Angeli, T. R. et al. Loss of interstitial cells of Cajal and patterns of gastric dysrhythmia in patients with chronic unexplained nausea and vomiting. Gastroenterology 149, 56–66.e5 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  6. O'Grady, G. et al. Origin and propagation of human gastric slow-wave activity defined by high-resolution mapping. Am. J. Physiol. Gastrointest. Liver Physiol. 299, G585–G592 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lammers, W. J. Normal and abnormal electrical propagation in the small intestine. Acta Physiol. (Oxf.) 213, 349–359 (2015).

    Article  CAS  Google Scholar 

  8. Lammers, W. J., Ver Donck, L., Stephen, B., Smets, D. & Schuurkes, J. A. 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).

    Article  CAS  PubMed  Google Scholar 

  9. Nakayama, S. Frequency analysis may distinguish the effects of calcium antagonists on mechanical and electrical activity. Neurogastroenterol. Motil. 24, 397; author reply 398 (2012).

    Article  CAS  PubMed  Google Scholar 

  10. O'Grady, G. Gastrointestinal extracellular electrical recordings: fact or artifact? Neurogastroenterol. Motil. 24, 1–6 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. O'Grady, G., Pullan, A. J. & Cheng, L. K. The analysis of human gastric pacemaker activity. J. Physiol. 590, 1299–1300; author reply 1301–1302 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  12. O'Grady, G., Angeli, T., Du, P. & Cheng, L. K. Concerning the validity of gastrointestinal extracellular recordings. Physiol. Rev. 95, 691–692 (2015).

    Article  PubMed  Google Scholar 

  13. Sanders, K. M., Ward, S. M. & Koh, S. D. Reply to O'Grady et al. Physiol. Rev. 95, 693–694 (2015).

    Article  PubMed  Google Scholar 

  14. Chowdhury, R. H. et al. Surface electromyography signal processing and classification techniques. Sensors (Basel) 13, 12431–12466 (2013).

    Article  Google Scholar 

  15. Bayguinov, O., Hennig, G. W. & Sanders, K. M. Movement based artifacts may contaminate extracellular electrical recordings from gastrointestinal muscles. Neurogastroenterol. Motil. 23, 1029–1042 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Park, K. J. et al. Spatial and temporal mapping of pacemaker activity in interstitial cells of Cajal in mouse ileum in situ. Am. J. Physiol. 290, C1411–C1427 (2006).

    Article  CAS  Google Scholar 

  17. Szurszewski, J. H. in Physiology of the Gastrointestinal Tract (ed. Johnson, L. R.) 1435–1466 (Raven Press, 1981).

    Google Scholar 

  18. Sanders, K. M., Ward, S. M. & Koh, S. D. Interstitial cells: regulators of smooth muscle function. Physiol. Rev. 94, 859–907 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Vogalis, F., Publicover, N. G., Hume, J. R. & Sanders, K. M. Relationship between calcium current and cytosolic calcium in canine gastric smooth muscle cells. Am. J. Physiol. 260, C1012–C1018 (1991).

    Article  CAS  PubMed  Google Scholar 

  20. Ozaki, H., Stevens, R. J., Blondfield, D. P., Publicover, N. G. & Sanders, K. M. Simultaneous measurement of membrane potential, cytosolic Ca2+, and tension in intact smooth muscles. Am. J. Physiol. 260, C917–C925 (1991).

    Article  CAS  PubMed  Google Scholar 

  21. Sanders, K. M., Koh, S. D., Ro, S. & Ward, S. M. Regulation of gastrointestinal motility-insights from smooth muscle biology. Nat. Rev. Gastroenterol. Hepatol. 9, 633–645 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  23. Koh, S. D., Ward, S. M. & Sanders, K. M. Ionic conductances regulating the excitability of colonic smooth muscles. Neurogastroenterol. Motil. 24, 705–718 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Bülbring, E. Smooth muscle potentials recorded in the taenia coli of the guineapig. J. Physiol. 123, 55P–56P (1954).

    Article  PubMed  Google Scholar 

  25. Dickens, E. J., Hirst, G. D. & Tomita, T. Identification of rhythmically active cells in guinea-pig stomach. J. Physiol. 514, 515–531 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kito, Y., Kurahashi, M., Mitsui, R., Ward, S. M. & Sanders, K. M. Spontaneous transient hyperpolarizations in the rabbit small intestine. J. Physiol. 592, 4733–4745 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kito, Y., Mitsui, R., Ward, S. M. & Sanders, K. M. Characterization of slow waves generated by myenteric interstitial cells of Cajal of the rabbit small intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 308, G378–G388 (2015).

    Article  CAS  PubMed  Google Scholar 

  28. Kito, Y. & Suzuki, H. Properties of pacemaker potentials recorded from myenteric interstitial cells of Cajal distributed in the mouse small intestine. J. Physiol. 553, 803–818 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kito, Y., Ward, S. M. & Sanders, K. M. Pacemaker potentials generated by interstitial cells of Cajal in the murine intestine. Am. J. Physiol. Cell Physiol. 288, C710–C720 (2005).

    Article  CAS  PubMed  Google Scholar 

  30. Cousins, H. M., Edwards, F. R., Hickey, H., Hill, C. E. & Hirst, G. D. Electrical coupling between the myenteric interstitial cells of Cajal and adjacent muscle layers in the guinea-pig gastric antrum. J. Physiol. 550, 829–844 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Sanders, K. M., Stevens, R., Burke, E. & Ward, S. M. Slow waves actively propagate at submucosal surface of circular layer in canine colon. Am. J. Physiol. 259, G258–G263 (1990).

    Article  CAS  PubMed  Google Scholar 

  32. Bortoff, A. Configuration of intestinal slow waves obtained by monopolar recording techniques. Am. J. Physiol. 213, 157–162 (1967).

    Article  CAS  PubMed  Google Scholar 

  33. Hoffman, B. F., Cranefield, P. F., Lepeschkin, E., Surawicz, B. & Herrlich, H. C. Comparison of cardiac monophasic action potentials recorded by intracellular and suction electrodes. Am. J. Physiol. 196, 1297–1301 (1959).

    Article  CAS  PubMed  Google Scholar 

  34. Szurszewski, J. H. Mechanism of action of pentagastrin and acetylcholine on the longitudinal muscle of the canine antrum. J. Physiol. 252, 335–361 (1975).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sarna, S. K. The gold standard for interpretation of slow wave frequency in in vitro and in vivo recordings by extracellular electrodes. J. Physiol. 591, 4373–4374 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Daniel, E. E. The electrical and contractile activity of the pyloric region in dogs and the effects of drugs. Gastroenterology 49, 403–418 (1965).

    Article  CAS  PubMed  Google Scholar 

  37. Daniel, E. E., Honour, A. J. & Bogoch, A. Electrical activity of the longitudinal muscle of dog small intestine studied in vivo using microelectrodes. Am. J. Physiol. 198, 113–118 (1960).

    Article  CAS  PubMed  Google Scholar 

  38. Kelly, K. A., Code, C. F. & Elveback, L. R. Patterns of canine gastric electrical activity. Am. J. Physiol. 217, 461–470 (1969).

    Article  CAS  PubMed  Google Scholar 

  39. Szurszewski, J. H. A migrating electric complex of canine small intestine. Am. J. Physiol. 217, 1757–1763 (1969).

    Article  CAS  PubMed  Google Scholar 

  40. Lammers, W. J., al-Kais, A., Singh, S., Arafat, K. & el-Sharkawy, T. Y. Multielectrode mapping of slow-wave activity in the isolated rabbit duodenum. J. Appl. Physiol. 74, 1454–1461 (1993).

    Article  CAS  PubMed  Google Scholar 

  41. Erickson, J. C. et al. Falling-edge, variable threshold (FEVT) method for the automated detection of gastric slow wave events in high-resolution serosal electrode recordings. Ann. Biomed. Eng. 38, 1511–1529 (2010).

    Article  PubMed  Google Scholar 

  42. Angeli, T. R. et al. The bioelectrical basis and validity of gastrointestinal extracellular slow wave recordings. J. Physiol. 591, 4567–4579 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hille, B. Ion Channels of Excitable Membranes (Sinauer Associates Inc, 2001).

    Google Scholar 

  44. Connor, J. A., Prosser, C. L. & Weems, W. A. A study of pace-maker activity in intestinal smooth muscle. J. Physiol. 240, 671–701 (1974).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Ordog, T. et al. Quantitative analysis by flow cytometry of interstitial cells of Cajal, pacemakers, and mediators of neurotransmission in the gastrointestinal tract. Cytometry A 62, 139–149 (2004).

    Article  PubMed  Google Scholar 

  46. Furness, J. B. The enteric nervous system and neurogastroenterology. Nat. Rev. Gastroenterol. Hepatol. 9, 286–294 (2012).

    Article  CAS  PubMed  Google Scholar 

  47. el-Sharkawy, T. Y., Morgan, K. G. & Szurszewski, J. H. Intracellular electrical activity of canine and human gastric smooth muscle. J. Physiol. 279, 291–307 (1978).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Nakayama, S., Ohishi, R., Sawamura, K., Watanabe, K. & Hirose, K. Microelectrode array evaluation of gut pacemaker activity in wild-type and W/W(v) mice. Biosens. Bioelectron. 25, 61–67 (2009).

    Article  CAS  PubMed  Google Scholar 

  49. Seerden, T. C., Lammers, W. J., De Winter, B. Y., De Man, J. G. & Pelckmans, P. A. Spatiotemporal electrical and motility mapping of distension-induced propagating oscillations in the murine small intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 289, G1043–G1051 (2005).

    Article  CAS  PubMed  Google Scholar 

  50. Bass, P., Code, C. F. & Lambert, E. H . Electric activity of gastroduodenal junction. Am. J. Physiol. 201, 587–592 (1961).

    Article  CAS  PubMed  Google Scholar 

  51. Papasova, M. & Boev, K. in Physiology of Smooth Muscle (eds Bulbring, E. & Shuba, M. F.) 209–216 (Raven Press, 1976).

    Google Scholar 

  52. el-Sharkawy, T. Y. & Szurszewski, J. H. Modulation of canine antral circular smooth muscle by acetylcholine, noradrenaline and pentagastrin. J. Physiol. 279, 309–320 (1978).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Hennig, G. W. et al. Propagation of pacemaker activity in the guinea-pig antrum. J. Physiol. 556, 585–599 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Paskaranandavadivel, N., O'Grady, G., Du, P. & Cheng, L. K. Comparison of filtering methods for extracellular gastric slow wave recordings. Neurogastroenterol. Motil. 25, 79–83 (2013).

    Article  PubMed  Google Scholar 

  55. Youm, J. B. et al. A mathematical model of pacemaker activity recorded from mouse small intestine. Philos. Trans. A Math. Phys. Eng. Sci. 364, 1135–1154 (2006).

    Article  CAS  PubMed  Google Scholar 

  56. Edwards, F. R. & Hirst, G. D. An electrical description of the generation of slow waves in the antrum of the guinea-pig. J. Physiol. 564, 213–232 (2005).

    Article  CAS  PubMed  Google Scholar 

  57. Goto, K., Matsuoka, S. & Noma, A. Two types of spontaneous depolarizations in the interstitial cells freshly prepared from the murine small intestine. J. Physiol. 559, 411–422 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Imtiaz, M. S., von der Weid, P. Y. & van Helden, D. F. Synchronization of Ca2+ oscillations: a coupled oscillator-based mechanism in smooth muscle. FEBS J. 277, 278–285 (2010).

    Article  CAS  PubMed  Google Scholar 

  59. van Helden, D. F., Laver, D. R., Holdsworth, J. & Imtiaz, M. S. Generation and propagation of gastric slow waves. Clin. Exp. Pharmacol. Physiol. 37, 516–524 (2010).

    Article  CAS  PubMed  Google Scholar 

  60. Singh, R. D. et al. Ano1, a Ca2+-activated Cl channel, coordinates contractility in mouse intestine by Ca2+ transient coordination between interstitial cells of Cajal. J. Physiol. 592, 4051–4068 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Aliev, R. R., Richards, W. & Wikswo, J. P. A simple nonlinear model of electrical activity in the intestine. J. Theor. Biol. 204, 21–28 (2000).

    Article  CAS  PubMed  Google Scholar 

  62. Buist, M. L., Corrias, A. & Poh, Y. C. A model of slow wave propagation and entrainment along the stomach. Ann. Biomed. Eng. 38, 3022–3030 (2010).

    Article  PubMed  Google Scholar 

  63. Pullan, A., Cheng, L., Yassi, R. & Buist, M. Modelling gastrointestinal bioelectric activity. Prog. Biophys. Mol. Biol. 85, 523–550 (2004).

    Article  PubMed  Google Scholar 

  64. Du, P. et al. The impact of surgical excisions on human gastric slow wave conduction, defined by high-resolution electrical mapping and in silico modeling. Neurogastroenterol. Motil. 27, 1409–1422 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Du, P., Paskaranandavadivel, N., O'Grady, G., Tang, S. J. & Cheng, L. K. A theoretical study of the initiation, maintenance and termination of gastric slow wave re-entry. Math. Med. Biol. 32, 405–423 (2014).

    PubMed  PubMed Central  Google Scholar 

  66. Kim, J. H., Du, P. & Cheng, L. K. Reconstruction of normal and abnormal gastric electrical sources using a potential based inverse method. Physiol. Meas. 34, 1193–1206 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Lammers, W. J. et al. Slow wave propagation and plasticity of interstitial cells of Cajal in the small intestine of diabetic rats. Exp. Physiol. 96, 1039–1048 (2011).

    Article  PubMed  Google Scholar 

  68. O'Grady, G. et al. Rapid high-amplitude circumferential slow wave propagation during normal gastric pacemaking and dysrhythmias. Neurogastroenterol. Motil. 24, e299–e312 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Hirst, G. D., Garcia-Londono, A. P. & Edwards, F. R. Propagation of slow waves in the guinea-pig gastric antrum. J. Physiol. 571, 165–177 (2006).

    Article  PubMed  Google Scholar 

  70. Dinning, P. G., Arkwright, J. W., Gregersen, H., O'Grady, G. & Scott, S. M. Technical advances in monitoring human motility patterns. Neurogastroenterol. Motil. 22, 366–380 (2010).

    Article  CAS  PubMed  Google Scholar 

  71. Baker, S. A. et al. Spontaneous Ca2+ transients in interstitial cells of Cajal located within the deep muscular plexus of the murine small intestine. J. Physiol. 594, 3317–3338 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Rhee, P. L. et al. Analysis of pacemaker activity in the human stomach. J. Physiol. 589, 6105–6118 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors are grateful to Y. Bayguinov for providing the images in Fig. 2 and Y. Shen and Y.-D. Luo from the Departments of Electrical and Biomedical Engineering at the University of Nevada, USA, for discussions and help with the signal processing used in Fig. 5. The authors are grateful to Y. Kito (Department of Pharmacology, Saga University, Japan) for providing the slow-wave data used in Fig. 5. The authors are also grateful to R. Mathias (State University of New York at Stony Brook, USA), D. Eisner (University of Manchester, UK) and A. Rich (State University of New York at Brockport, USA) for reading and commenting on this Perspectives article. The authors are supported by: R37 DK-40569 to K.M.S; R01 DK-057236 to S.M.W. and P01 DK-41315 to K.M.S. and S.M.W.

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed equally to this work.

Corresponding author

Correspondence to Kenton M. Sanders.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sanders, K., Ward, S. & Hennig, G. Problems with extracellular recording of electrical activity in gastrointestinal muscle. Nat Rev Gastroenterol Hepatol 13, 731–741 (2016). https://doi.org/10.1038/nrgastro.2016.161

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrgastro.2016.161

  • Springer Nature Limited

This article is cited by

Navigation