ArticleThe Journal of biological chemistry2008
Isoform-specific inhibition of TRPC4 channel by phosphatidylinositol 4,5-bisphosphate.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
94 citing papers in PubMed, 170 citations in OpenAlex.
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Targeting TRPC channels for control of arthritis-induced bone erosion.Science advances · 2025Article
- Molecular evolution of TRPC4 regulatory sequences supports a role in mammalian thermoregulatory adaptation.PeerJ · 2025Article
- Direct modulation of TRPC ion channels by Gα proteins.Frontiers in physiology · 2024Review
- The function of alternative splicing in the proteome: rewiring protein interactomes to put old functions into new contexts.Nature structural & molecular biology · 2023Review
- Innate cocaine-seeking vulnerability arising from loss of serotonin-mediated aversive effects of cocaine in rats.Cell reports · 2023Article
- Negative self-regulation of transient receptor potential canonical 4 by the specific interaction with phospholipase C-δ1.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2023Article
- Ionic signalling mechanisms involved in neurokinin-3 receptor-mediated augmentation of fear-potentiated startle response in the basolateral amygdala.The Journal of physiology · 2022Article
- How filopodia respond to calcium in the absence of a calcium-binding structural protein: non-channel functions of TRP.Cell communication and signaling : CCS · 2022Article
- The normalized slope conductance as a tool for quantitative analysis of current-voltage relations.Biophysical journal · 2022Article
- Involvement of TRPC5 channels, inwardly rectifying KThe Journal of physiology · 2021Article
- Species-Specific Regulation of TRPM2 by PI(4,5)PInternational journal of molecular sciences · 2021Article
- Intracellular activation of full-length human TREK-1 channel by hypoxia, high lactate, and low pH denotes polymodal integration by ischemic factors.Pflugers Archiv : European journal of physiology · 2021Article
- Functions of Muscarinic Receptor Subtypes in Gastrointestinal Smooth Muscle: A Review of Studies with Receptor-Knockout Mice.International journal of molecular sciences · 2021Review
- Nitric oxide resets kisspeptin-excited GnRH neurons via PIP2 replenishment.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- TRPC4 as a coincident detector of GCurrent opinion in physiology · 2020Article
- The Expression of Cold-Inducible RNA-Binding Protein mRNA in Sow Genital Tract Is Modulated by Natural Mating, But Not by Seminal Plasma.International journal of molecular sciences · 2020Article
- Intracellular acidification facilitates receptor-operated TRPC4 activation through PLCδ1 in a CaThe Journal of physiology · 2020Article
- TRPC channels: Structure, function, regulation and recent advances in small molecular probes.Pharmacology & therapeutics · 2020Review
- TRPC1 Regulates the Activity of a Voltage-Dependent Nonselective Cation Current in Hippocampal CA1 Neurons.Cells · 2020Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
Abstract
Full-length transient receptor potential (TRP) cation channel TRPC4alpha and shorter TRPC4beta lacking 84 amino acids in the cytosolic C terminus are expressed in smooth muscle and endothelial cells where they regulate membrane potential and Ca(2+) influx. In common with other "classical" TRPCs, TRPC4 is activated by G(q)/phospholipase C-coupled receptors, but the underlying mechanism remains elusive. Little is also known about any isoform-specific channel regulation. Here we show that TRPC4alpha but not TRPC4beta was strongly inhibited by intracellularly applied phosphatidylinositol 4,5-bisphosphate (PIP(2)). In contrast, several other phosphoinositides (PI), including PI(3,4)P(2), PI(3,5)P(2), and PI(3,4,5)P(3), had no effect or even potentiated TRPC4alpha indicating that PIP(2) inhibits TRPC4alpha in a highly selective manner. We show that PIP(2) binds to the C terminus of TRPC4alpha but not that of TRPC4beta in vitro. Its inhibitory action was dependent on the association of TRPC4alpha with actin cytoskeleton as it was prevented by cytochalasin D treatment or by the deletion of the C-terminal PDZ-binding motif (Thr-Thr-Arg-Leu) that links TRPC4 to F-actin through the sodium-hydrogen exchanger regulatory factor and ezrin. PIP(2) breakdown appears to be a required step in TRPC4alpha channel activation as PIP(2) depletion alone was insufficient for channel opening, which additionally required Ca(2+) and pertussis toxin-sensitive G(i/o) proteins. Thus, TRPC4 channels integrate a variety of G-protein-dependent stimuli, including a PIP(2)/cytoskeleton dependence reminiscent of the TRPC4-like muscarinic agonist-activated cation channels in ileal myocytes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.