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Regulation of gastrointestinal motility—insights from smooth muscle biology

Nature Reviews Gastroenterology & Hepatology volume 9, pages 633–645 (2012)Cite this article

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Abstract

Gastrointestinal motility results from coordinated contractions of the tunica muscularis, the muscular layers of the alimentary canal. Throughout most of the gastrointestinal tract, smooth muscles are organized into two layers of circularly or longitudinally oriented muscle bundles. Smooth muscle cells form electrical and mechanical junctions between cells that facilitate coordination of contractions. Excitation–contraction coupling occurs by Ca2+ entry via ion channels in the plasma membrane, leading to a rise in intracellular Ca2+. Ca2+ binding to calmodulin activates myosin light chain kinase; subsequent phosphorylation of myosin initiates cross-bridge cycling. Myosin phosphatase dephosphorylates myosin to relax muscles, and a process known as Ca2+ sensitization regulates the activity of the phosphatase. Gastrointestinal smooth muscles are 'autonomous' and generate spontaneous electrical activity (slow waves) that does not depend upon input from nerves. Intrinsic pacemaker activity comes from interstitial cells of Cajal, which are electrically coupled to smooth muscle cells. Patterns of contractile activity in gastrointestinal muscles are determined by inputs from enteric motor neurons that innervate smooth muscle cells and interstitial cells. Here we provide an overview of the cells and mechanisms that generate smooth muscle contractile behaviour and gastrointestinal motility.

Key Points

  • Gastrointestinal motility occurs by the coordinated contractions of the tunica muscula ris, which forms the outer wall of the alimentary canal from the distal oesophagus to the external anal sphincter

  • Excitation–contraction coupling results from Ca2+ entry into smooth muscle cells, Ca2+ release from the sarcoplasmic reticulum, activation of myosin light chain kinase and phosphorylation of the regulatory light chains of myosin

  • Contractile force is tuned by Ca2+ sensitization mechanisms that balance rates of myosin phosphorylation and dephosphorylation

  • Interstitial cells of Cajal (ICC) provide spontaneous pacemaker activity in gastrointestinal muscles; ICC and PDGFRα+ cells also contribute to mediation of inputs from enteric motor neurons

  • Gastrointestinal motility patterns are highly integrated behaviours requiring coordination between smooth muscle cells and utilizing regulatory inputs from interstitial cells, neurons, and endocrine and immune cells

  • Therapeutic regulation and tissue engineering of gastrointestinal motility is proving difficult

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Figure 1: Regulation of gastrointestinal motility.
Figure 2: Major cellular mechanisms controlling contraction in gastrointestinal smooth muscle cells.
Figure 3: miRNA-mediated SMC remodelling.

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Acknowledgements

The work of these authors and time spent on this Review was supported by grants from the NIDDK: R37 DK40569 (K. M. Sanders), P01 DK41315 (K. M. Sanders, S. D. Koh and S. M. Ward) and P20 GM103513 (S. Ro). The authors are grateful for discussions with Dr B. Perrino and his comments on the manuscript. We apologize if we have neglected the work of some investigators; research on gastrointestinal smooth muscle biology is bountiful and could not be reviewed exhaustively in this limited space.

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  1. Department of Physiology and Cell Biology, University of Nevada School of Medicine, Anderson Medical Sciences, Reno, 89557, NV, USA

    Kenton M. Sanders, Sang Don Koh, Seungil Ro & Sean M. Ward

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  1. Kenton M. Sanders
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K. M. Sanders contributed to all aspects of this manuscript. S. D. Koh and S. M. Ward contributed to the discussion of content and reviewing/editing the manuscript. S. Ro contributed to writing and reviewing/editing the manuscript.

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Sanders, K., Koh, S., Ro, S. et al. Regulation of gastrointestinal motility—insights from smooth muscle biology. Nat Rev Gastroenterol Hepatol 9, 633–645 (2012). https://doi.org/10.1038/nrgastro.2012.168

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