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Ca2+ Signaling Is the Basis for Pacemaker Activity and Neurotransduction in Interstitial Cells of the GI Tract

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The Enteric Nervous System II

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1383))

Abstract

Years ago gastrointestinal motility was thought to be due to interactions between enteric nerves and smooth muscle cells (SMCs) in the tunica muscularis. Thus, regulatory mechanisms controlling motility were either myogenic or neurogenic. Now we know that populations of interstitial cells, c-Kit+ (interstitial cells of Cajal or ICC), and PDGFRα+ cells (formerly “fibroblast-like” cells) are electrically coupled to SMCs, forming the SIP syncytium. Pacemaker and neurotransduction functions are provided by interstitial cells through Ca2+ release from the endoplasmic reticulum (ER) and activation of Ca2+-activated ion channels in the plasma membrane (PM). ICC express Ca2+-activated Cl− channels encoded by Ano1. When activated, Ano1 channels produce inward current and, therefore, depolarizing or excitatory effects in the SIP syncytium. PDGFRα+ cells express Ca2+-activated K+ channels encoded by Kcnn3. These channels generate outward current when activated and hyperpolarizing or membrane-stabilizing effects in the SIP syncytium. Inputs from enteric and sympathetic neurons regulate Ca2+ transients in ICC and PDGFRα+ cells, and currents activated in these cells conduct to SMCs and regulate contractile behaviors. ICC also serve as pacemakers, generating slow waves that are the electrophysiological basis for gastric peristalsis and intestinal segmentation. Pacemaker types of ICC express voltage-dependent Ca2+ conductances that organize Ca2+ transients, and therefore Ano1 channel openings, into clusters that define the amplitude and duration of slow waves. Ca2+ handling mechanisms are at the heart of interstitial cell function, yet little is known about what happens to Ca2+ dynamics in these cells in GI motility disorders.

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Acknowledgments

Writing of this paper and much of the data reviewed was supported by R01 DK120759 to KMS and SAB and R01 DK-091336 to KMS and MK.

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Authors and Affiliations

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

    Kenton M. Sanders, Salah A. Baker, Bernard T. Drumm & Masaaki Kurahashi

  2. Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Iowa, Iowa, Iowa City, USA

    Masaaki Kurahashi

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  1. Kenton M. Sanders
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  2. Salah A. Baker
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  3. Bernard T. Drumm
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  4. Masaaki Kurahashi
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Correspondence to Kenton M. Sanders .

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Editors and Affiliations

  1. College of Medicine & Public Health Flinders Medical Centre, Adelaide, SA, Australia

    Nick J. Spencer

  2. College of Medicine & Public Health Flinders Medical Centre, Adelaide, SA, Australia

    Marcello Costa

  3. South Australian Health & Medical Research Institute, Adelaide, SA, Australia

    Stuart M. Brierley

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Sanders, K.M., Baker, S.A., Drumm, B.T., Kurahashi, M. (2022). Ca2+ Signaling Is the Basis for Pacemaker Activity and Neurotransduction in Interstitial Cells of the GI Tract. In: Spencer, N.J., Costa, M., Brierley, S.M. (eds) The Enteric Nervous System II. Advances in Experimental Medicine and Biology, vol 1383. Springer, Cham. https://doi.org/10.1007/978-3-031-05843-1_22

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