Open AccessPropulsive colonic contractions are mediated by inhibition-driven poststimulus responses that originate in interstitial cells of Cajal
Author(s) -
Sang Don Koh,
Bernard T. Drumm,
Hsin-I Lu,
Hyun Jin Kim,
Sungwoo Ryoo,
Heung Up Kim,
Ji Yeon Lee,
PoongLyul Rhee,
Qianqian Wang,
Thomas W. Gould,
Dante J. Heredia,
Brian A. Perrino,
Sung Jin Hwang,
Sean M. Ward,
Kenton M. Sanders
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2123020119
Subject(s) - interstitial cell of cajal , excitatory postsynaptic potential , peristalsis , inhibitory postsynaptic potential , neuroscience , stimulation , cholinergic , reflex , biology , acetylcholine , electrophysiology , myenteric plexus , chemistry , anatomy , smooth muscle , endocrinology , immunohistochemistry , immunology
Significance The peristaltic reflex elicits colonic migrating motor complexes (CMMCs) that are thought to be generated by enteric excitatory neurons stimulating smooth muscle cells (SMCs). We found that atropine did not block CMMCs and present a concept showing that poststimulus excitatory responses following nitrergic responses in interstitial cells of Cajal (ICC) are responsible for initiation of CMMCs. Ca2+ transients in ICC are inhibited by nitrergic stimulation. After the inhibitory period, Ca2+ transients are increased, activating currents that are conducted to SMCs and initiate propagated contractions. Poststimulus excitation generated by ICC explains the properties of CMMCs. This is important because current therapeutic manipulation of colonic transit is typically directed at strengthening cholinergic responses, whereas targeting nitrergic responses may be more suitable.