Propulsive colonic contractions are mediated by inhibition-driven poststimulus responses that originate in interstitial cells of Cajal

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. Ca 2+ transients in ICC are inhibited by nitrergic stimulation. After the inhibitory period, Ca 2+ 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.