ArticleThe Journal of biological chemistry2012
Selective Gαi subunits as novel direct activators of transient receptor potential canonical (TRPC)4 and TRPC5 channels.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed.
- Transient receptor potential canonical (TRPC) channels in diabetes and associated complications.Channels (Austin, Tex.) · 2026Review
- Functional and structural basis of a hypermorphic TRPC3 variant.Science advances · 2026Article
- Direct crosstalk between GPCRs and ion channels via G proteins.Experimental & molecular medicine · 2025Review
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Thermo-TRP regulation by endogenous factors and its physiological function at core body temperature.Physiological reports · 2025Review
- Transient Receptor Potential Canonical 5 (TRPC5): Regulation of Heart Rate and Protection against Pathological Cardiac Hypertrophy.Biomolecules · 2024Article
- The scale of zebrafish pectoral fin buds is determined by intercellular K+ levels and consequent Ca2+-mediated signaling via retinoic acid regulation of Rcan2 and Kcnk5b.PLoS biology · 2024Article
- Article
- Direct modulation of TRPC ion channels by Gα proteins.Frontiers in physiology · 2024Review
- Unique responses of the fixed stoichiometric TRPC1-TRPC5 concatemer to G proteins.Frontiers in physiology · 2024Article
- Inhibition of TRPC4 channel activity in colonic myocytes by tricyclic antidepressants disrupts colonic motility causing constipation.Journal of cellular and molecular medicine · 2022Article
- TRPC4 and GIRK channels underlie neuronal coding of firing patterns that reflect GProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Monitoring TRPC7 Conformational Changes by BRET Following GPCR Activation.International journal of molecular sciences · 2022Article
- Canonical transient receptor potential channels and their modulators: biology, pharmacology and therapeutic potentials.Archives of pharmacal research · 2021Review
- Article
- Article
- Article
- TRPC4 as a coincident detector of GCurrent opinion in physiology · 2020Article
- N-benzhydryl quinuclidine compounds are a potent and Src kinase-independent inhibitor of NALCN channels.British journal of pharmacology · 2020Article
- Intracellular acidification facilitates receptor-operated TRPC4 activation through PLCδ1 in a CaThe Journal of physiology · 2020Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
The ubiquitous transient receptor potential canonical (TRPC) channels function as non-selective, Ca(2+)-permeable channels and mediate numerous cellular functions. It is commonly assumed that TRPC channels are activated by stimulation of Gα(q)-PLC-coupled receptors. However, whether the Gα(q)-PLC pathway is the main regulator of TRPC4/5 channels and how other Gα proteins may regulate these channels are poorly understood. We previously reported that TRPC4/TRPC5 can be activated by Gα(i). In the current work, we found that Gα(i) subunits, rather than Gα(q), are the primary and direct activators of TRPC4 and TRPC5. We report a novel molecular mechanism in which TRPC4 is activated by several Gα(i) subunits, most prominently by Gα(i2), and TRPC5 is activated primarily by Gα(i3). Activation of Gα(i) by the muscarinic M2 receptors or expression of the constitutively active Gα(i) mutants equally and fully activates the channels. Moreover, both TRPC4 and TRPC5 are activated by direct interaction of their conserved C-terminal SESTD (SEC14-like and spectrin-type domains) with the Gα(i) subunits. Two amino acids (lysine 715 and arginine 716) of the TRPC4 C terminus were identified by structural modeling as mediating the interaction with Gα(i2). These findings indicate an essential role of Gα(i) proteins as novel activators for TRPC4/5 and reveal the molecular mechanism by which G-proteins activate the channels.
Indexed as
Identifiers
What OpenQuestion holds
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.