ArticleThe Journal of physiology2007
Three distinct muscarinic signalling pathways for cationic channel activation in mouse gut smooth muscle cells.
Article in The Journal of physiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 41 citations in OpenAlex.
- Cryo-EM structure of the heteromeric TRPC1/TRPC4 channel.Nature structural & molecular biology · 2025Article
- Molecular architecture of the GαNature communications · 2023Article
- General anaesthesia-related complications of gut motility with a focus on cholinergic mechanisms, TRP channels and visceral pain.Frontiers in physiology · 2023Article
- Contribution of Postjunctional M2 Muscarinic Receptors to Cholinergic Nerve-Mediated Contractions of Murine Airway Smooth Muscle.Function (Oxford, England) · 2022Article
- Functions of Muscarinic Receptor Subtypes in Gastrointestinal Smooth Muscle: A Review of Studies with Receptor-Knockout Mice.International journal of molecular sciences · 2021Review
- Analysis of interaction between intracellular spermine and transient receptor potential canonical 4 channel: multiple candidate sites of negatively charged amino acids for the inward rectification of transient receptor potential canonical 4.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2020Article
- Review
- TRPC1 as a negative regulator for TRPC4 and TRPC5 channels.Pflugers Archiv : European journal of physiology · 2019Review
- Involvement of transient receptor potential melastatin 4 channels in the resting membrane potential setting and cholinergic contractile responses in mouse detrusor and ileal smooth muscles.The Journal of veterinary medical science · 2019Article
- Possible antagonistic effects of the TRPC4 channel blocker ML204 on MThe Journal of veterinary medical science · 2018Article
- Intracellular spermine blocks TRPC4 channel via electrostatic interaction with C-terminal negative amino acids.Pflugers Archiv : European journal of physiology · 2016Article
- Inhibitory effects of SKF96365 on the activities of K(+) channels in mouse small intestinal smooth muscle cells.The Journal of veterinary medical science · 2016Article
- Functional alterations in gut contractility after connexin36 ablation and evidence for gap junctions forming electrical synapses between nitrergic enteric neurons.FEBS letters · 2014Article
- Isoform- and receptor-specific channel property of canonical transient receptor potential (TRPC)1/4 channels.Pflugers Archiv : European journal of physiology · 2014Article
- Selective Gαi subunits as novel direct activators of transient receptor potential canonical (TRPC)4 and TRPC5 channels.The Journal of biological chemistry · 2012Article
- Impaired M3 and enhanced M2 muscarinic receptor contractile function in a streptozotocin model of mouse diabetic urinary bladder.Naunyn-Schmiedeberg's archives of pharmacology · 2010Article
- Multiple muscarinic pathways mediate the suppression of voltage-gated Ca2+ channels in mouse intestinal smooth muscle cells.British journal of pharmacology · 2009Article
- The guinea pig ileum lacks the direct, high-potency, M(2)-muscarinic, contractile mechanism characteristic of the mouse ileum.Naunyn-Schmiedeberg's archives of pharmacology · 2009Article
- Deletion of TRPC4 and TRPC6 in mice impairs smooth muscle contraction and intestinal motility in vivo.Gastroenterology · 2009Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Using mutant mice genetically lacking certain subtypes of muscarinic receptor, we have studied muscarinic signal pathways mediating cationic channel activation in intestinal smooth muscle cells. In cells from M2 subtype-knockout (M2-KO) or M3-KO mice, carbachol (100 microM) evoked a muscarinic cationic current (mI(Cat)) as small as approximately 10% of mI(Cat) in wild-type (WT) cells. No appreciable current was evoked in M2/M3 double-KO cells. All mutant type cells preserved normal G-protein-cationic channel coupling. The M3-KO and WT mI(Cat) each showed a U-shaped current-voltage (I-V) relationship, whereas the M2-KO mI(Cat) displayed a linear I-V relationship. Channel analysis in outside-out patches recognized 70-pS and 120-pS channels as the major muscarinic cationic channels. Active patches of M2-KO cells exhibited both 70-pS and 120-pS channel activity usually together, either of which consisted of brief openings (the respective mean open times O(tau) = 0.55 and 0.23 ms). In contrast, active M3-KO patches showed only 70-pS channel activity, which had three open states (O(tau) = 0.55, 3.1 and 17.4 ms). In WT patches, besides the M2-KO and M3-KO types, another type of channel activity was also observed that consisted of 70-pS channel openings with four open states (O(tau) = 0.62, 2.7, 16.9 and 121.1 ms), and patch current of this channel activity showed a U-shaped I-V curve similar to the WT mI(Cat). The present results demonstrate that intestinal myocytes are endowed with three distinct muscarinic pathways mediating cationic channel activation and that the M2/M3 pathway targeting 70-pS channels, serves as the major contributor to mI(Cat) generation. The delineation of this pathway is consistent with the formation of a functional unit by the M2-Go protein and the M3-PLC systems predicted to control cationic channels.
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