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, Dieter Saur

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

169 Zitate (Scopus)

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.

OriginalspracheEnglisch
Aufsatznummer1630
FachzeitschriftNature Communications
Jahrgang4
DOIs
PublikationsstatusVeröffentlicht - 2013

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