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

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.