title: Interstitial cells of Cajal integrate excitatory and inhibitory neurotransmission with intestinal slow-wave activity.
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-Kit(CreERT2) 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.
authors.affiliation: Department of Internal Medicine 2, Klinikum rechts der Isar, Technische Universität München, München 81675, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Klein
authors.forename: Barbara
authors.initials: B
authors.lastname: Seidler
authors.forename: Anna
authors.initials: A
authors.lastname: Kettenberger
authors.forename: Andrei
authors.initials: A
authors.lastname: Sibaev
authors.forename: Michael
authors.initials: M
authors.lastname: Rohn
authors.forename: Robert
authors.initials: R
authors.lastname: Feil
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Allescher
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Vanderwinden
authors.forename: Franz
authors.initials: F
authors.lastname: Hofmann
authors.forename: Michael
authors.initials: M
authors.lastname: Schemann
authors.forename: Roland
authors.initials: R
authors.lastname: Rad
authors.forename: Martin A
authors.initials: MA
authors.lastname: Storr
authors.forename: Roland M
authors.initials: RM
authors.lastname: Schmid
authors.forename: Günter
authors.initials: G
authors.lastname: Schneider
authors.forename: Dieter
authors.initials: D
authors.lastname: Saur
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D062965:Cyclic GMP-Dependent Protein Kinase Type I / Q000235:genetics; D017615:Enteric Nervous System / Q000502:physiology*; D056885:Interstitial Cells of Cajal / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009435:Synaptic Transmission
chemical_list: D062965:Cyclic GMP-Dependent Protein Kinase Type I; C569720:Prkg1 protein, mouse
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