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Excitatory cholinergic responses in mouse colon intramuscular interstitial cells of Cajal are due to enhanced Ca2+ release via M3 receptor activation.


ABSTRACT: Colonic intramuscular interstitial cells of Cajal (ICC-IM) are associated with cholinergic varicosities, suggesting a role in mediating excitatory neurotransmission. Ca2+ release in ICC-IM activates Ano1, a Ca2+ -activated Cl- conductance, causing tissue depolarization and increased smooth muscle excitability. We employed Ca2+ imaging of colonic ICC-IM in situ, using mice expressing GCaMP6f in ICC to evaluate ICC-IM responses to excitatory neurotransmission. Expression of muscarinic type 2, 3 (M2 , M3 ), and NK1 receptors were enriched in ICC-IM. NK1 receptor agonists had minimal effects on ICC-IM, whereas neostigmine and carbachol increased Ca2+ transients. These effects were reversed by DAU 5884 (M3 receptor antagonist) but not AF-DX 116 (M2 receptor antagonist). Electrical field stimulation (EFS) in the presence of L-NNA and MRS 2500 enhanced ICC-IM Ca2+ transients. Responses were blocked by atropine or DAU 5884, but not AF-DX 116. ICC-IM responses to EFS were ablated by inhibiting Ca2+ stores with cyclopiazonic acid and reduced by inhibiting Ca2+ influx via Orai channels. Contractions induced by EFS were reduced by an Ano1 channel antagonist, abolished by DAU 5884, and unaffected by AF-DX 116. Colonic ICC-IM receive excitatory inputs from cholinergic neurons via M3 receptor activation. Enhancing ICC-IM Ca2+ release and Ano1 activation contributes to excitatory responses of colonic muscles.

SUBMITTER: Drumm BT 

PROVIDER: S-EPMC7790594 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Excitatory cholinergic responses in mouse colon intramuscular interstitial cells of Cajal are due to enhanced Ca<sup>2+</sup> release via M<sub>3</sub> receptor activation.

Drumm Bernard T BT   Rembetski Benjamin E BE   Huynh Kaitlin K   Nizar Aqeel A   Baker Salah A SA   Sanders Kenton M KM  

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20200615 8


Colonic intramuscular interstitial cells of Cajal (ICC-IM) are associated with cholinergic varicosities, suggesting a role in mediating excitatory neurotransmission. Ca<sup>2+</sup> release in ICC-IM activates Ano1, a Ca<sup>2+</sup> -activated Cl<sup>-</sup> conductance, causing tissue depolarization and increased smooth muscle excitability. We employed Ca<sup>2+</sup> imaging of colonic ICC-IM in situ, using mice expressing GCaMP6f in ICC to evaluate ICC-IM responses to excitatory neurotransmi  ...[more]

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