Research article summary (published 19 Jun 2009):

Deletion of TRPC4 and TRPC6 in mice impairs smooth muscle contraction and intestinal motility in vivo.

Full Abstract

BACKGROUND & AIMS: Downstream effects of muscarinic receptor stimulation in intestinal smooth muscle include contraction and intestinal transit. We thought to determine whether classic transient receptor potential (TRPC) channels integrate the intracellular signaling cascades evoked by the stimulated receptors and thereby contribute to the control of the membrane potential, Ca-influx, and cell responses. METHODS: We created trpc4-, trpc6-, and trpc4/trpc6-gene-deficient mice and analyzed them for intestinal smooth muscle function in vitro and in vivo. RESULTS: In intestinal smooth muscle cells TRPC4 forms a 55 pS cation channel and underlies more than 80% of the muscarinic receptor-induced cation current (mI(CAT)). The residual mI(CAT) depends on the expression of TRPC6, indicating that TRPC6 and TRPC4 determine mI(CAT) channel activity independent of other channel subunits. In TRPC4-deficient ileal myocytes the carbachol-induced membrane depolarizations are diminished greatly and the atropine-sensitive contraction elicited by acetylcholine release from excitatory motor neurons is reduced greatly. Additional deletion of TRPC6 aggravates these effects. Intestinal transit is slowed down in mice lacking TRPC4 and TRPC6. CONCLUSIONS: In intestinal smooth muscle cells TRPC4 and TRPC6 channels are gated by muscarinic receptors and are responsible for mI(CAT). They couple muscarinic receptors to depolarization of intestinal smooth muscle cells and voltage-activated Ca(2+)-influx and contraction, and thereby accelerate small intestinal motility in vivo.

Author information

Author/s: Tsvilovskyy, Volodymyr V (VV); Zholos, Alexander V (AV); Aberle, Thomas (T); Philipp, Stephan E (SE); Dietrich, Alexander (A); Zhu, Michael X (MX); Birnbaumer, Lutz (L); Freichel, Marc (M); Flockerzi, Veit (V);

Affiliation: Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg, Germany.

Grants: DK081654 (Agency:NIDDK NIH HHS) ; Z01-ES-101684 (Agency:NIEHS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Gastroenterology (Gastroenterology), published in United States. (Language: eng)

Reference: 2009-Oct; vol 137 (issue 4) : pp 1415-24

Dates: Created 2009/10/05; Completed 2009/10/15;

PMID: 19549525, status: MEDLINE (last retrieved date: 10/15/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

Comments and Corrections

CommentIn: Gastroenterology. 2009 Oct;137(4):1211-4. (PMID: 19717126)

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Acetylcholine - metabolism Animals Atropine - pharmacology Calcium Channels, L-Type - metabolism Calcium Signaling - drug effects Carbachol - pharmacology Cholinergic Agonists - pharmacology Electric Stimulation Enteric Nervous System - metabolism Gastrointestinal Motility - drug effects Ileum - drug effects; innervation; metabolism

Ion Channel Gating Membrane Potentials Mice Mice, Inbred C57BL Mice, Knockout Muscarinic Antagonists - pharmacology Muscle Contraction - drug effects Muscle, Smooth - drug effects; innervation; metabolism Myocytes, Smooth Muscle - metabolism Receptors, Muscarinic - metabolism TRPC Cation Channels - deficiency; genetics

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Calcium Channels, L-Type (0) ; Cholinergic Agonists (0) ; Muscarinic Antagonists (0) ; Receptors, Muscarinic (0) ; TRPC Cation Channels (0) ; TRPC4 ion channel (0) ; Trpc6 protein, mouse (0) ; Atropine (51-55-8) ; Carbachol (51-83-2) ; Acetylcholine (51-84-3)

Related articles

These are the most related articles currently in our database:

• Prejunctional M1 and postjunctional M3 muscarinic receptors in the circular muscle of the guinea-pig ileum. 27 Feb 1995
• Antagonism by imidazoline-type drugs of muscarinic and other receptors in the guinea-pig ileum. 29 Jun 2006
• Involvement of cholinergic neurons in orexin-induced contraction of guinea pig ileum. 25 Sep 2002
• Multiple motor effects of ATP and their inhibition by P purinoceptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid in the small intestine of the guinea-pig. 29 Apr 2006
• Effects of a new cholecystokinin antagonist (GE 410) on the smooth muscle of the guinea pig ileum. 13 Oct 1990
• Neurotensin contracts the guinea-pig longitudinal ileal smooth muscle by inducing acetylcholine release. 29 Jun 1979
• Caerulein receptors on the cholinergic neurons in guinea-pig ileum. 30 Dec 1990
• Site of action of galanin in the cholinergic transmission of guinea pig small intestine. 13 Sep 1995
• Immunohistochemical localisation of pre-synaptic muscarinic receptor subtype-2 (M2r) in the enteric nervous system of guinea-pig ileum. 3 Feb 2008
• Muscarinic receptor-activated cationic channels in murine ileal myocytes. 5 Aug 2006

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a larger map of 100+ related articles.