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Data from: Neuronal regulation of myenteric interstitial cells of Cajal (ICC-MY) in the colon

Baker, Sal1; Drumm, Bernard2; Karwa, Manushri1; Thompson, Katy3; Smith, Benjamin1; Sanders, Kenton1

Published Jul 21, 2025 on Dryad. https://doi.org/10.5061/dryad.31zcrjf0k

Data files

Jul 21, 2025 version files 22.72 MB

Abstract

Interstitial cells of Cajal (ICC) generate contractile patterns of colonic motility. We investigated innervation of ICC within the plane of the myenteric plexus (ICC-MY) in proximal colon using mice expressing GCaMP6f in ICC. ICC-MY generated localized Ca2+ transients that couple to activation of ANO1 channels, a Ca2+-activated Cl- conductance. ICC are electrically coupled to SMCs, so activation or suppression of currents in ICC affects excitability of SMCs. ICC-MY displayed tonic inhibition, as the neurotoxin, TTX, increased the frequency of Ca2+ transients. Tonic inhibition was mimicked by a nitric oxide donor, NONOate, and by a guanylate cyclase agonist (Bay 58-2667). In contrast, ODQ mimicked the effects of TTX, increasing Ca2+ transients. Carbachol (CCh) increased Ca2+ transients in ICC-MY, and these effects were mediated by M3 muscarinic receptors. Neostigmine also increased Ca2+ transients, suggesting there is tonic activation of enteric excitatory neurons in colonic muscles. Substance P and antagonists of NK1 and NK2 receptors had no effect on Ca2+ transients in ICC-MY. Electrical field stimulation (EFS), under conditions that emphasized excitatory neural responses, enhanced Ca2+ transients, and these effects were blocked by atropine or an M3 receptor antagonist (DAU 5884). EFS in the presence of atropine caused inhibition of Ca2+ via release of NO. Cessation of nitrergic stimulation resulted in a substantial increase in Ca2+ transients, known as post-stimulus excitation. In summary, ICC-MY, important for the generation of propulsive contractions in the colon, are innervated by excitatory (cholinergic) and inhibitory (nitrergic) motor neurons, and these inputs regulate the excitability of these cells.