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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.
FASEB J. 2020 Jun 15 [Online ahead of print]FJ

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.

Authors+Show Affiliations

Department of Physiology and Cell Biology, Reno School of Medicine, University of Nevada, Reno, NV, USA. Department of Life & Health Science, Dundalk Institute of Technology, Dundalk, Ireland.Department of Physiology and Cell Biology, Reno School of Medicine, University of Nevada, Reno, NV, USA.Department of Physiology and Cell Biology, Reno School of Medicine, University of Nevada, Reno, NV, USA.Department of Physiology and Cell Biology, Reno School of Medicine, University of Nevada, Reno, NV, USA.Department of Physiology and Cell Biology, Reno School of Medicine, University of Nevada, Reno, NV, USA.Department of Physiology and Cell Biology, Reno School of Medicine, University of Nevada, Reno, NV, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32539213

Citation

Drumm, Bernard T., et al. "Excitatory Cholinergic Responses in Mouse Colon Intramuscular Interstitial Cells of Cajal Are Due to Enhanced Ca2+ Release Via M3 Receptor Activation." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 2020.
Drumm BT, Rembetski BE, Huynh K, et al. Excitatory cholinergic responses in mouse colon intramuscular interstitial cells of Cajal are due to enhanced Ca2+ release via M3 receptor activation. FASEB J. 2020.
Drumm, B. T., Rembetski, B. E., Huynh, K., Nizar, A., Baker, S. A., & Sanders, K. M. (2020). Excitatory cholinergic responses in mouse colon intramuscular interstitial cells of Cajal are due to enhanced Ca2+ release via M3 receptor activation. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology. https://doi.org/10.1096/fj.202000672R
Drumm BT, et al. Excitatory Cholinergic Responses in Mouse Colon Intramuscular Interstitial Cells of Cajal Are Due to Enhanced Ca2+ Release Via M3 Receptor Activation. FASEB J. 2020 Jun 15; PubMed PMID: 32539213.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Excitatory cholinergic responses in mouse colon intramuscular interstitial cells of Cajal are due to enhanced Ca2+ release via M3 receptor activation. AU - Drumm,Bernard T, AU - Rembetski,Benjamin E, AU - Huynh,Kaitlin, AU - Nizar,Aqeel, AU - Baker,Salah A, AU - Sanders,Kenton M, Y1 - 2020/06/15/ PY - 2020/03/21/received PY - 2020/05/01/revised PY - 2020/05/11/accepted PY - 2020/6/16/entrez KW - Ca2+ imaging KW - Ca2+ stores KW - SIP syncytium KW - c-Kit KW - cholinergic KW - gastrointestinal motility KW - optogenetics JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J. N2 - 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. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/32539213/Excitatory_cholinergic_responses_in_mouse_colon_intramuscular_interstitial_cells_of_Cajal_are_due_to_enhanced_Ca2+_release_via_M3_receptor_activation L2 - https://doi.org/10.1096/fj.202000672R DB - PRIME DP - Unbound Medicine ER -
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