Interstitial cells of Cajal mediate nitrergic inhibitory neurotransmission in the murine gastrointestinal tract.
Nitric oxide (NO) is a major inhibitory neurotransmitter in the gastrointestinal (GI) tract. Its main effector, NO-sensitive guanylyl cyclase (NO-GC), is expressed in several GI cell types, including smooth muscle cells (SMC), interstitial cells of Cajal (ICC), and fibroblast-like cells. Up to date, the interplay between neurons and these cells to initiate a nitrergic inhibitory junction potential (IJP) is unclear. Here, we investigate the origin of the nitrergic IJP in murine fundus and colon. IJPs were determined in fundus and colon SMC of mice lacking NO-GC globally (GCKO) and specifically in SMC (SM-GCKO), ICC (ICC-GCKO), and both SMC/ICC (SM/ICC-GCKO). Nitrergic IJP was abolished in ICC-GCKO fundus and reduced in SM-GCKO fundus. In the colon, the amplitude of nitrergic IJP was reduced in ICC-GCKO, whereas nitrergic IJP in SM-GCKO was reduced in duration. These results were corroborated by loss of the nitrergic IJP in global GCKO. In conclusion, our results prove the obligatory role of NO-GC in ICC for the initiation of an IJP. NO-GC in SMC appears to enhance the nitrergic IJP, resulting in a stronger and prolonged hyperpolarization in fundus and colon SMC, respectively. Thus NO-GC in both cell types is mandatory to induce a full nitrergic IJP. Our data from the colon clearly reveal the nitrergic IJP to be biphasic, resulting from individual inputs of ICC and SMC.
Physiologisches Institut, Universität Würzburg, Würzburg, Germany;
Barbara
B
Lies
Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Instituto de Salud Carlos III, Barcelona, Spain; and.
Víctor
V
Gil
Physiologisches Institut, Universität Würzburg, Würzburg, Germany;
Dieter
D
Groneberg
II. Medizinische Klinik und Poliklinik, Technische Universität München, München, Germany.
Barbara
B
Seidler
II. Medizinische Klinik und Poliklinik, Technische Universität München, München, Germany.
Dieter
D
Saur
Physiologisches Institut, Universität Würzburg, Würzburg, Germany;
Erhard
E
Wischmeyer
Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, CIBERehd, Instituto de Salud Carlos III, Barcelona, Spain; and.
Marcel
M
Jiménez
Physiologisches Institut, Universität Würzburg, Würzburg, Germany; andreas.friebe@uni-wuerzburg.de.
Andreas
A
Friebe
D000818:Animals; D003106:Colon / Q000294:innervation*; D005748:Gastric Fundus / Q000294:innervation*; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism; D053444:Inhibitory Postsynaptic Potentials; D056885:Interstitial Cells of Cajal / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009433:Neural Inhibition; D026602:Nitrergic Neurons / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009435:Synaptic Transmission; D013997:Time Factors
D009569:Nitric Oxide; D006162:Guanylate Cyclase
cGMP; gastrointestinal smooth muscle; inhibitory junction potential; knockout mice; nitric oxide