Interstitial cells of Cajal integrate excitatory and inhibitory neurotransmission with intestinal slow-wave activity

Sabine Klein, Barbara Seidler, Anna Kettenberger, Andrei Sibaev, Michael Rohn, Robert Feil, Hans-Dieter Allescher, Jean-Marie Vanderwinden, Franz Hofmann, Michael Schemann, Roland Rad, Martin A. Storr, Roland M. Schmid, Günter Schneider and Dieter Saur ()
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Sabine Klein: Klinikum rechts der Isar, Technische Universität München
Barbara Seidler: Klinikum rechts der Isar, Technische Universität München
Anna Kettenberger: Klinikum rechts der Isar, Technische Universität München
Andrei Sibaev: Ludwig-Maximilians-Universität München
Michael Rohn: Lehrstuhl für Humanbiologie, Technische Universität München
Robert Feil: Interfaculty Institute of Biochemistry, University of Tübingen
Hans-Dieter Allescher: Zentrum für Innere Medizin, Klinikum Garmisch-Partenkirchen
Jean-Marie Vanderwinden: Université Libre de Bruxelles (ULB), ULB Neuroscience Institute (UNI), Neurophysiology lab
Franz Hofmann: Forschergruppe 923, Institut für Pharmakologie und Toxikologie, Klinikum rechts der Isar, Technische Universität München
Michael Schemann: Lehrstuhl für Humanbiologie, Technische Universität München
Roland Rad: Wellcome Trust Sanger Institute, Genome Campus
Martin A. Storr: Ludwig-Maximilians-Universität München
Roland M. Schmid: Klinikum rechts der Isar, Technische Universität München
Günter Schneider: Klinikum rechts der Isar, Technische Universität München
Dieter Saur: Klinikum rechts der Isar, Technische Universität München

Nature Communications, 2013, vol. 4, issue 1, 1-9

Abstract: Abstract The enteric nervous system contains excitatory and inhibitory neurons, which control contraction and relaxation of smooth muscle cells as well as gastrointestinal motor activity. Little is known about the exact cellular mechanisms of neuronal signal transduction to smooth muscle cells in the gut. Here we generate a c-KitCreERT2 knock-in allele to target a distinct population of pacemaker cells called interstitial cells of Cajal. By genetic loss-of-function studies, we show that interstitial cells of Cajal, which generate spontaneous electrical slow waves and thus rhythmic contractions of the smooth musculature, are essential for transmission of signals from enteric neurons to gastrointestinal smooth muscle cells. Interstitial cells of Cajal, therefore, integrate excitatory and inhibitory neurotransmission with slow-wave activity to orchestrate peristaltic motor activity of the gut. Impairment of the function of interstitial cells of Cajal causes severe gastrointestinal motor disorders. The results of our study show at the genetic level that these disorders are not only due to loss of slow-wave activity but also due to disturbed neurotransmission.

Date: 2013
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DOI: 10.1038/ncomms2626

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