Affinage

TRPC3

Short transient receptor potential channel 3 · UniProt Q13507

Length
921 aa
Mass
105.5 kDa
Annotated
2026-04-28
100 papers in source corpus 47 papers cited in narrative 46 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRPC3 is a non-selective cation channel that functions as a central integrator of receptor-activated phospholipase C signaling, transducing diacylglycerol production into Ca²⁺ and Na⁺ influx across diverse cell types including neurons, cardiomyocytes, vascular smooth muscle, immune cells, and secretory epithelia. The channel is directly gated by DAG in a membrane-delimited, PKC-independent manner, with PIP₂ serving as a required co-activator and Src kinase playing an obligatory role in receptor-coupled activation (PMID:9930701, PMID:17942152, PMID:15271991). TRPC3 assembles as a homotetramer or heterotetramer with TRPC1, TRPC6, or TRPC7 and forms macromolecular signaling complexes with NCX1, RACK1, IP₃ receptors, Nox2, and Orai1, coupling ion flux to downstream processes including cardiac excitation-contraction coupling, cerebrovascular tone regulation, hypothalamic glucose sensing, BDNF/TrkB neurotrophin signaling, T-cell activation, and mechanotransduction in sensory neurons and cochlear hair cells (PMID:17129578, PMID:18755685, PMID:10677043, PMID:22724068, PMID:27899482). Channel activity is negatively regulated by PKC phosphorylation at Ser712 and by N-linked glycosylation pattern, while surface expression is controlled by a C-terminal CIRB domain, PLCγ1 via an intermolecular PH-domain interaction, and cholesterol loading; a gain-of-function T635A mutation in the S4–S5 linker (Moonwalker) causes constitutive overactivation and cerebellar Purkinje cell degeneration leading to ataxia (PMID:15533987, PMID:12970363, PMID:15744307, PMID:24797279).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1999 High

    The fundamental gating mechanism of TRPC3 was established: DAG directly activates the channel in a membrane-delimited manner independent of PKC, resolving the long-standing question of how PLC-coupled receptors open TRP channels without store depletion.

    Evidence Patch-clamp electrophysiology with DAG application and PKC inhibitor controls in HEK293 cells expressing hTRPC3

    PMID:9930701

    Open questions at the time
    • Structural basis of DAG binding site unknown at this time
    • Whether PIP₂ is required for DAG-dependent gating not yet addressed
  2. 1999 High

    TRPC3 was identified as the channel mediating BDNF/TrkB neurotrophin signaling in CNS neurons, establishing its first native physiological role beyond heterologous expression systems.

    Evidence Immunohistochemistry, electrophysiology with dominant-negative and overexpression strategies in pontine neurons

    PMID:10677043

    Open questions at the time
    • Identity of the endogenous TRPC3 complex in neurons unknown
    • Whether TRPC3 acts alone or in heteromeric assemblies in this context
  3. 2003 High

    Multiple regulatory determinants of TRPC3 were mapped: DAG metabolism controls activation duration, the C-terminal CIRB region is required for plasma membrane targeting (independent of actual IP₃R/CaM binding), and the single N-glycosylation site on extracellular loop e1 accounts for TRPC3's high constitutive activity relative to TRPC6.

    Evidence Pharmacological DAG metabolism inhibition, deletion mutagenesis with confocal imaging in IP₃R-null DT40 cells, reciprocal glycosylation site engineering between TRPC3 and TRPC6 with electrophysiology

    PMID:12606542 PMID:12730194 PMID:12970363

    Open questions at the time
    • Molecular identity of CIRB-dependent trafficking machinery unknown
    • Whether glycosylation differences explain tissue-specific constitutive activity not tested
  4. 2004 High

    Two key regulatory phosphorylation mechanisms were defined: Src kinase is obligatory for receptor/DAG-coupled activation, and PKC phosphorylation at Ser712 provides negative feedback, answering how kinase signaling tunes TRPC3 channel activity.

    Evidence Src inhibitors, dominant-negative Src, Src-deficient cell complementation; S712A mutagenesis with phosphorylation and Ca²⁺ assays in HEK293 cells

    PMID:15271991 PMID:15533987

    Open questions at the time
    • Direct Src phosphorylation site on TRPC3 not mapped
    • Whether Src and PKC regulation are interdependent not resolved
  5. 2004 High

    TRPC3 was shown to mediate receptor-induced vasoconstriction in native cerebral arteries, establishing it as a physiological regulator of vascular tone distinct from TRPC6.

    Evidence Antisense knockdown of TRPC3 with patch clamp and arterial diameter measurements in intact cerebral arteries

    PMID:15604128

    Open questions at the time
    • Whether TRPC3 mediates myogenic tone (as opposed to receptor-operated tone) unclear
    • Heteromeric channel composition in native smooth muscle unknown
  6. 2005 High

    Two surface-expression control mechanisms were discovered: PLCγ1 binds TRPC3 via a split (gestalt) PH-domain interaction controlling surface delivery, and TRPC1/TRPC3/TRPC7 form a native heteromeric complex mediating store-operated Ca²⁺ entry, revealing that TRPC3 function depends on both trafficking and subunit composition.

    Evidence Co-immunoprecipitation and lipid-binding assays for PLCγ1–TRPC3 PH domain; siRNA knockdown with co-IP for heteromeric complex in HEK293 cells

    PMID:15744307 PMID:15972814

    Open questions at the time
    • Whether the PLCγ1–TRPC3 PH interaction is regulated by lipids in vivo not determined
    • Stoichiometry of heteromeric assemblies undefined
  7. 2006 High

    TRPC3 was established as a cardiac signaling hub: it physically couples with NCX1 in cardiomyocytes to drive PLC-dependent Ca²⁺ entry via Na⁺ loading, and separately couples with RyR1 in skeletal muscle to modulate excitation-contraction coupling gain.

    Evidence Reciprocal co-IP and GST pull-down in cardiac tissue with dominant-negative TRPC3; shRNA knockdown with Ca²⁺ release and E-C coupling assays in primary myotubes

    PMID:16484216 PMID:17012351 PMID:17129578

    Open questions at the time
    • Direct binding interface between TRPC3 and NCX1 not structurally defined
    • Whether TRPC3–RyR1 coupling is direct or scaffold-mediated unknown
  8. 2007 High

    PIP₂ was shown to directly gate TRPC3 in excised patches and to be required for DAG-dependent activation, resolving how lipid environment controls channel open probability.

    Evidence Excised inside-out patch-clamp with direct PIP₂ and DAG analog application

    PMID:17942152

    Open questions at the time
    • PIP₂ binding site on TRPC3 not identified
    • Interplay between PIP₂ depletion by PLC and PIP₂ requirement for gating not fully modeled
  9. 2008 High

    The TRPC3–RACK1–IP₃R ternary complex was mapped to specific N-terminal residues (E232, D233, E240, E244), and IP₃ receptors on the SR were shown to activate sarcolemmal TRPC3 independently of Ca²⁺ release, establishing a junctional signaling mechanism in cerebral artery myocytes.

    Evidence Site-directed mutagenesis of RACK1-binding residues with surface biotinylation; shRNA knockdown of TRPC3 with FRET-based SR Ca²⁺ and patch clamp in cerebral arteries

    PMID:18388325 PMID:18755685

    Open questions at the time
    • Whether IP₃R conformational coupling to TRPC3 involves direct contact or an intermediate scaffold
    • Structural basis of RACK1–TRPC3 interface at atomic level unknown
  10. 2009 High

    TRPC3 was identified as essential for T-cell receptor-dependent Ca²⁺ entry (by genetic complementation of T-cell mutants), shown to organize a macromolecular Orai1–STIM1–RACK1–IP₃R complex, and found to be inhibited by NO/cGMP/PKG signaling in vascular smooth muscle, broadening its roles to immune activation and vasorelaxation.

    Evidence Genetic rescue of Ca²⁺-deficient T-cell mutants with TRPC3 cDNA; siRNA with co-IP in HEK293; patch clamp with intracellular antibody blockade and co-IP of native TRPC1/TRPC3 complex in smooth muscle

    PMID:12736256 PMID:19502552 PMID:20022948

    Open questions at the time
    • Whether TRPC3 scaffolding of Orai1–IP₃R is independent of its ion conductance not fully dissected
    • PKG phosphorylation site(s) on TRPC3 not identified
  11. 2009 High

    Pyr3 was identified as the first selective TRPC3 inhibitor through photoaffinity labeling proving direct binding, providing a pharmacological tool that enabled subsequent in vivo studies.

    Evidence Photoaffinity labeling, structure-activity relationship, electrophysiology in DT40 B cells and cardiomyocytes

    PMID:19289841

    Open questions at the time
    • Pyr3 binding site on TRPC3 not structurally resolved
    • Selectivity over all TRP family members not comprehensively profiled
  12. 2011 High

    Genetic and pharmacological evidence demonstrated TRPC3 as the major Ca²⁺ influx channel in exocrine secretory cells, with Trpc3⁻/⁻ mice and Pyr3 protecting against pancreatitis, and WNK4 kinase was identified as a negative regulator of TRPC3 in vascular smooth muscle linking to hypertension genetics.

    Evidence Trpc3⁻/⁻ mice with cerulein pancreatitis model and Pyr3; WNK4 siRNA and PHAII mutant expression with myography in mesenteric arteries

    PMID:21354153 PMID:21670282

    Open questions at the time
    • Whether WNK4 directly phosphorylates TRPC3 or acts indirectly not determined
    • Therapeutic window for Pyr3 in pancreatitis not established
  13. 2012 High

    TRPC3/TRPC6 double knockout revealed their joint requirement for rapidly-adapting mechanotransduction in DRG sensory neurons and cochlear hair cells, establishing TRPC3 as a mechanosensory channel component.

    Evidence Single and double KO mice with DRG patch clamp, auditory brainstem responses, outer hair cell recording, and heterologous reconstitution

    PMID:22724068

    Open questions at the time
    • Whether TRPC3/TRPC6 are the pore-forming subunits of the mechanotransduction complex or accessory subunits
    • Force-transmission mechanism to the channel unknown
  14. 2014 High

    The Moonwalker gain-of-function mutation (T635A in S4–S5 linker) linked constitutive TRPC3 overactivation to Purkinje cell degeneration and cerebellar ataxia, identifying this channel as essential for cerebellar neuron survival and connecting gating to disease.

    Evidence Moonwalker mouse model with electrophysiology and Purkinje cell histology; subsequent lipidomics showing disrupted ceramide metabolism partially rescued by ceramide treatment

    PMID:24797279 PMID:25908616

    Open questions at the time
    • Whether human TRPC3 gain-of-function mutations cause ataxia not established
    • How constitutive Ca²⁺ influx disrupts ceramide homeostasis mechanistically
  15. 2015 High

    TRPC3 was shown to have a channel-activity-independent scaffolding function: it stabilizes Nox2 in cardiomyocytes to amplify mechanical stress-induced ROS and fibrosis, and combined TRPC3/TRPC6 deletion (but not single deletion) protects against pressure-overload cardiac hypertrophy, demonstrating functional redundancy.

    Evidence Co-IP of TRPC3–Nox2, ROS measurements, pressure-overload in TRPC3-overexpressing and KO mice; double TRPC3/TRPC6 KO with TAC and echocardiography

    PMID:24453217 PMID:25631581 PMID:28936433

    Open questions at the time
    • Nox2 binding domain on TRPC3 not mapped
    • Whether scaffolding versus ion-conducting functions can be pharmacologically separated
  16. 2016 High

    Conditional TRPC3 knockout in the hypothalamus demonstrated its requirement for glucose-excited neuron responses and systemic glucose homeostasis, expanding TRPC3's physiological roles to central metabolic sensing.

    Evidence Constitutive and conditional TRPC3 KO mice with MBH neuron Ca²⁺ imaging, intracerebroventricular glucose, food intake, and insulin secretion measurements

    PMID:27899482

    Open questions at the time
    • Upstream signal linking glucose metabolism to TRPC3 gating in MBH neurons not identified
    • Whether DAG/PLC pathway mediates glucose detection through TRPC3 in this context
  17. 2018 High

    The cryo-EM structure of TRPC3 at 4.4 Å revealed a tetrameric two-layer architecture with ankyrin repeat and coiled-coil domains forming the cytosolic bell, and identified the BTDM inhibitor-binding pocket between S5–S6 and the voltage-sensor-like domain, providing the first structural framework for channel gating and drug design.

    Evidence Single-particle cryo-EM of human TRPC3 with bound BTDM inhibitor

    PMID:29700422

    Open questions at the time
    • DAG-bound or PIP₂-bound open-state structure not yet solved
    • Structural basis of Src or PKC regulation not visualized
  18. 2022 High

    Two DAG-binding sites (L1 and L2) were functionally mapped using structure-guided mutagenesis and MD simulations; L2-site mutations promote a sensitized channel state, revealing a lipid-dependent molecular memory mechanism for repetitive DAG exposure.

    Evidence Structure-guided mutagenesis with photoswitchable DAG (OptoBI-1) electrophysiology and MD simulations

    PMID:35604352

    Open questions at the time
    • High-resolution cryo-EM with DAG bound at L1 and L2 not yet available
    • Physiological relevance of L2-dependent sensitization in native cells not demonstrated
  19. 2022 High

    TRPC3 was identified as a negative regulator of IP₃R-mediated Ca²⁺ release; its downregulation in senescence promotes mitochondrial Ca²⁺ oscillations and enhanced OXPHOS, revealing a non-canonical role in controlling intracellular Ca²⁺ store dynamics.

    Evidence TRPC3 re-expression in senescent fibroblasts with mitochondrial Ca²⁺ and OXPHOS measurements, xenograft model

    PMID:35177596

    Open questions at the time
    • Mechanism by which TRPC3 suppresses IP₃R-mediated release (scaffolding vs. ion flux) not resolved
    • Whether this applies across cell types beyond fibroblasts

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions remain: the high-resolution structure of TRPC3 in DAG/PIP₂-bound open states, the direct Src phosphorylation site, the structural interface for Nox2 scaffolding, whether channel-independent functions can be pharmacologically dissected from ion conduction, and whether human TRPC3 gain-of-function mutations cause cerebellar ataxia.
  • Open-state structure with bound DAG/PIP₂ not solved
  • Src phosphorylation site on TRPC3 not identified
  • Human genetic disease causality for TRPC3 not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0008289 lipid binding 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 7
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-382551 Transport of small molecules 4 R-HSA-112316 Neuronal System 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 2 R-HSA-397014 Muscle contraction 2
Partners
NCX1NOX2ORAI1PLCG1RACK1TRPC1TRPC6TRPC7
Complex memberships
TRPC1/TRPC3/TRPC7 heterotetramerTRPC3-NCX1 signaling complexTRPC3-Nox2 complexTRPC3-RACK1-IP3R ternary complex

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 TRPC3 is a non-selective cation channel directly activated by diacylglycerol (DAG) in a membrane-delimited, protein kinase C-independent manner, establishing it as a second-messenger-operated cation channel downstream of phospholipase C. Electrophysiology (patch clamp), DAG application, PKC inhibitor controls in HEK293 cells expressing hTRPC3 Nature High 9930701
2003 Receptor-mediated activation of TRPC3 in intact cells occurs via DAG production from phospholipase C, independently of G proteins, protein kinase C, or inositol 1,4,5-trisphosphate; DAG metabolism controls the duration of TRPC3 activation. Fluorescence Ca2+ imaging, pharmacological inhibitors, agonist dose-response, DAG metabolism inhibition in HEK293 cells stably expressing TRPC3 The Journal of biological chemistry High 12606542
1999 TRPC3 is highly enriched in CNS neurons, co-localizes with TrkB, and is required for BDNF/TrkB-induced PLC-dependent non-selective cation conductance in pontine neurons, establishing TRPC3 as a neurotrophin-activated channel in vivo. Immunohistochemistry, electrophysiology in pontine neurons, dominant-negative and overexpression strategies Neuron High 10677043
2004 Src kinase plays an obligatory role in receptor- and DAG-dependent activation of TRPC3; pharmacological inhibition of Src, dominant-negative Src, or Src-deficient cell lines abolish TRPC3 activation, which is restored by wild-type Src. Pharmacological Src inhibitors, dominant-negative Src expression, Src-deficient cell line complementation, Ca2+ entry assays in HEK293 cells The Journal of biological chemistry High 15271991
2004 Protein kinase C phosphorylates TRPC3 at Ser712, providing negative feedback regulation; mutation of Ser712 to alanine abolishes PKC-mediated inhibition and enhances agonist-stimulated Ca2+ entry. Site-directed mutagenesis (S712A), PMA treatment, in vivo phosphorylation assay, Ca2+ imaging in HEK293 cells Molecular pharmacology High 15533987
2003 The calmodulin/IP3 receptor-binding (CIRB) region in the C terminus of TRPC3 is required for plasma membrane targeting; internal deletion of this 20-amino acid region mislocalizes TRPC3 to intracellular compartments and abolishes channel activity, but the mechanism is independent of actual IP3 receptor or calmodulin binding. Confocal microscopy of fluorescent protein-tagged TRPC3 mutants, Ca2+ entry assays, expression in IP3 receptor-null DT40 cells The Journal of biological chemistry High 12730194
2003 N-linked glycosylation at a single extracellular loop (e1) site in TRPC3 confers considerable constitutive activity; engineering an additional glycosylation site (as in TRPC6) markedly reduces TRPC3 basal activity, identifying glycosylation pattern as a molecular determinant of constitutive vs. regulated channel behavior. In vitro mutagenesis of NXT motifs, immunoblotting, electrophysiology, and fluorescence imaging in HEK293 cells The Journal of biological chemistry High 12970363
2005 PLCγ1 binds to TRPC3 via an intermolecular PH domain interaction: a partial PH domain in PLCγ1 interacts with a complementary PH-like domain in TRPC3, controlling cell-surface expression of the channel. Co-immunoprecipitation, gestalt PH-domain algorithm, lipid binding assays, surface expression measurements Nature High 15744307
2005 Endogenous TRPC1, TRPC3, and TRPC7 assemble into a heteromeric complex that mediates a major component of store-operated Ca2+ entry in HEK-293 cells; co-immunoprecipitation confirmed the TRPC1-TRPC3-TRPC7 complex. siRNA knockdown, Ba2+ entry assay, co-immunoprecipitation The Journal of biological chemistry High 15972814
2006 TRPC3 physically and functionally couples with the Na+/Ca2+ exchanger NCX1 in cardiac myocytes; PLC stimulation triggers NCX-mediated Ca2+ entry dependent on TRPC3-mediated Na+ loading, and PLC activation promotes co-recruitment of TRPC3-NCX1 complex to the plasma membrane. Reciprocal co-immunoprecipitation, GST pull-down, surface biotinylation, dominant-negative TRPC3 expression, Ca2+ fluorimetry in rat cardiomyocytes Cardiovascular research High 17129578
2006 TRPC3 co-localizes with NCX1 and Na+/K+-ATPase in the axial transverse-axial tubular system of rat ventricular myocytes; reciprocal immunoprecipitation from native ventricle confirms TRPC3–NCX1 association (direct) but not TRPC3–NKA (indirect via NCX1). Western blot, immunofluorescence, reciprocal co-immunoprecipitation from rat/canine ventricle and Sf9 cells expressing defined protein combinations American journal of physiology. Heart and circulatory physiology High 17012351
2008 IP3 receptors on the sarcoplasmic reticulum activate sarcolemmal TRPC3 channels in cerebral artery myocytes, generating Na+ influx, membrane depolarization, voltage-dependent Ca2+ channel opening, and vasoconstriction independently of SR Ca2+ release. SR Ca2+ depletion (FRET-based D1ER indicator), shRNA knockdown of TRPC3, patch clamp, intravital Ca2+ imaging, pharmacological blockers in isolated cerebral arteries Circulation research High 18388325
2008 TRPC3 interacts with RACK1 via N-terminal residues Glu-232, Asp-233, Glu-240, and Glu-244; this interaction controls plasma membrane localization of TRPC3 and is required for agonist-induced recruitment of a TRPC3–RACK1–IP3R ternary complex, increased TRPC3 surface expression, and IP3-dependent Ca2+ release. Site-directed mutagenesis of RACK1-binding residues, co-immunoprecipitation, surface biotinylation, Ca2+ imaging in HEK293 cells The Journal of biological chemistry High 18755685
2006 TRPC3 functionally couples with RyR1 in skeletal muscle; TRPC3 knockdown reduces excitation-contraction coupling gain and RyR1 Ca2+ release channel activity without altering SR Ca2+ load, and alters expression of key triadic proteins (triadin, junctophilin-1, calsequestrin, TRPC1). Retroviral shRNA knockdown, Mn2+ influx, Fluo-4 Ca2+ imaging, caffeine-induced Ca2+ release, immunoblotting in mouse primary myotubes The Journal of biological chemistry High 16484216
2007 PIP2 directly activates TRPC3 channels in excised membrane patches; TRPC3 channels in the TRPC3/6/7 subfamily exhibit complex regulation by both DAG and PIP2, with PIP2 required for DAG-dependent activation. Excised inside-out patch clamp, PIP2 application, ATP application, cell-attached patch with DAG analog in TRPC3/6/7-expressing cells Cell calcium High 17942152
2009 Pyrazole compound Pyr3 selectively and directly inhibits TRPC3 channels; photoaffinity labeling demonstrates direct binding to the TRPC3 protein; structure-function studies identify the trichloroacrylic amide group as essential for TRPC3 selectivity. Electrophysiology, photoaffinity labeling, structure-activity relationship studies, Ca2+ imaging in DT40 B lymphocytes and cardiomyocytes Proceedings of the National Academy of Sciences of the United States of America High 19289841
2018 Cryo-EM structure of human TRPC3 at 4.4 Å resolution reveals a two-layer architecture with a bell-shaped cytosolic layer (N-terminal ankyrin repeats and C-terminal coiled-coil) supporting the transmembrane layer; extensive inter-subunit interactions of cytosolic domains mediate tetramer assembly; a high-affinity inhibitor (BTDM) wedges between the S5-S6 pore domain and voltage sensor-like domain to block channel opening. Single-particle cryo-EM at 4.4 Å resolution, structural comparison with TRPC6 inhibitor complex Cell research High 29700422
2004 TRPC3 mediates UTP/pyrimidine receptor-induced depolarization and constriction of cerebral artery smooth muscle cells; antisense knockdown of TRPC3 abolishes UTP-evoked whole-cell cationic currents and vasoconstriction without affecting myogenic (pressure-induced) responses, whereas TRPC6 antisense had no effect on UTP responses. Antisense oligodeoxynucleotides, patch clamp, arterial diameter measurements in intact cerebral arteries American journal of physiology. Heart and circulatory physiology High 15604128
2006 Cellular cholesterol loading activates TRPC3-dependent non-selective cation conductance and promotes surface expression of TRPC3; cholesterol and PLC stimulation each increase TRPC3 plasma membrane presentation, with cholesterol-induced expression being sustained versus transient PLC-mediated trafficking. Electrophysiology, dominant-negative TRPC3 with extracellular HA tag conferring antibody sensitivity, cholesterol loading in HEK293 cells The Biochemical journal Medium 16448384
2008 TRPM4b physically interacts with TRPC3 (identified by yeast two-hybrid and confirmed by co-immunoprecipitation), co-localizes at the plasma membrane, and overexpression of TRPM4b suppresses TRPC3-mediated whole-cell currents by >90% and abolishes store-operated Ca2+ entry. Yeast two-hybrid, co-immunoprecipitation, confocal microscopy, whole-cell patch clamp in HEK293T cells Biochemical and biophysical research communications Medium 18262493
2009 TRPC3 mediates the scaffolding interaction between Orai1 and the type I IP3 receptor; TRPC3 silencing prevents Orai1–type I IP3R association, attenuates RACK1–type I IP3R interaction, and reduces agonist-stimulated Ca2+ release and entry, placing TRPC3 as a central organizer of the Orai1–STIM1–TRPC3–RACK1–type I IP3R signaling complex. siRNA knockdown of TRPC3, co-immunoprecipitation, Ca2+ imaging in HEK293 cells The Journal of biological chemistry Medium 20022948
2017 β-arrestin-1-biased AT1R agonist (TRV120027) promotes recruitment of TRPC3 and PLCγ into the AT1R–β-arrestin-1 signaling complex at the plasma membrane; blocking the β-arrestin-1/PLCγ interaction with a TAT-P1 peptide abolishes TRV120027-induced TRPC3 activation and catecholamine secretion. Co-immunoprecipitation, TAT peptide blockade, Ca2+ influx measurements, catecholamine secretion assays Nature communications Medium 28181498
2011 TRPC3 is a major Ca2+ influx channel in pancreatic acini and salivary gland cells; genetic deletion or pharmacological inhibition of TRPC3 with Pyr3 protects these secretory epithelia from Ca2+-dependent cytotoxicity in acute pancreatitis and Sjögren syndrome models. Trpc3-/- mice, Pyr3 pharmacological inhibition, acute pancreatitis model (cerulein injection), Ca2+ signaling analysis Gastroenterology High 21354153
2011 WNK4 kinase restricts TRPC3-mediated Ca2+ influx in vascular smooth muscle cells; WNK4 depletion augments TRPC3-dependent Ca2+ entry and induces hypertrophic growth and vasoconstriction; PHAII-causing WNK4 mutations and kinase-dead mutants fail to inhibit TRPC3. siRNA knockdown of WNK4, WNK4 mutant expression, Ca2+ influx assays, myography in mesenteric arteries Proceedings of the National Academy of Sciences of the United States of America High 21670282
2012 TRPC3 and TRPC6 double knockout mice show deficits in rapidly-adapting mechanosensitive currents in sensory neurons and hearing loss; loss of TRPC3 alone shifts RA currents to intermediate-adapting; TRPC3 and TRPC6 co-expression in sensory neuron cell lines reconstitutes FM1-43-sensitive mechanically gated currents. Single/double KO mice, patch clamp of DRG neurons, auditory brainstem responses, outer hair cell mechanotransduction recording, FM1-43 uptake, heterologous reconstitution Open biology High 22724068
2015 TRPC3 forms a stable protein complex with NADPH oxidase 2 (Nox2) in cardiomyocytes, stabilizing Nox2 and amplifying mechanical stress-induced ROS signaling, leading to cardiac fibrosis; this channel activity-independent scaffolding function of TRPC3 is distinct from its ion-conducting role. Co-immunoprecipitation, ROS measurements, cardiac fibrosis assays in TRPC3-overexpressing and KO mice, pressure overload model Scientific reports (inferred from Frontiers review citing primary data) Medium 28790356 28936433
2015 TRPC3 promotes cardiac arrhythmogenesis through spatial coupling with NCX1: TRPC3 activation increases NCX current and elevates local Ca2+ near NCX1; excessive TRPC3 activation causes transient spatial uncoupling of TRPC3 and NCX1, leading to Ca2+ overload and arrhythmias. TRPC3-overexpressing mouse model, novel TRPC3 agonist GSK1702934A, patch clamp, Langendorff heart preparation, immunocytochemistry colocalization Cardiovascular research High 25631581
2009 TRPC3 mediates T-cell receptor-dependent Ca2+ entry in human T-lymphocytes; TRPC3 gene mutations in T-cell mutants defective in Ca2+ influx are accompanied by loss of TRPC3 expression, and reintroduction of TRPC3 cDNA rescues both Ca2+ currents and TCR-dependent signals. Genetic complementation of T-cell mutants with TRPC3 cDNA, electrophysiology, Ca2+ imaging The Journal of biological chemistry High 12736256
2022 TRPC3 acts as a negative regulator of IP3 receptor-mediated Ca2+ release; downregulation of TRPC3 in senescence promotes cytosolic/mitochondrial Ca2+ oscillations and elevates mitochondrial OXPHOS; re-expression of TRPC3 in senescent cells reduces mitochondrial Ca2+ load. TRPC3 re-expression in senescent fibroblasts, mitochondrial Ca2+ measurements, OXPHOS measurements, xenograft tumor model Nature communications High 35177596
2022 DAG interacts with two lipid-binding sites (L1 and L2) in TRPC3; MD simulations show rapid DAG accumulation at both sites; L2-site mutations (e.g., G652A) promote a sensitized channel state with faster activation kinetics upon repetitive DAG exposure, defining a lipid-dependent sensitization mechanism. Structure-guided mutagenesis, electrophysiology with photoswitchable DAG probe, molecular dynamics simulations EMBO reports High 35604352
2019 A photoswitchable DAG analog (OptoBI-1) enables light-controlled, lipid-metabolism-independent activation of TRPC3 channels; this tool demonstrated TRPC3-linked control of neuronal firing and endothelial Ca2+ transients in native cells. Azobenzene-based photoswitch chemistry, electrophysiology, Ca2+ imaging in endothelial cells and neurons Chemical science Medium 30997005
2014 TRPC3 gain-of-function Moonwalker mutation (T635A in the S4-S5 linker) causes constitutive channel overactivation, Purkinje cell and unipolar brush cell degeneration, and cerebellar ataxia, linking channel gating to cerebellar development. Genetic mouse model characterization, electrophysiology, histology of Purkinje cells Cerebellum High 24797279
2015 The Moonwalker TRPC3 gain-of-function mutation alters Ca2+ signaling in Purkinje cells and is coupled to disrupted lipid homeostasis (ceramide pathway); treatment with ceramide improves dendritic outgrowth of mutant Purkinje cells, revealing a TRPC3-calcium-lipid metabolism axis in cerebellar development. Laser-capture microdissection transcriptomics, lipidomics, organotypic cerebellar slice treatment with ceramide, dendritic morphology analysis Human molecular genetics Medium 25908616
2016 TRPC3 channels in mediobasal hypothalamus neurons are required for glucose-excited neuron responses to glucose; TRPC3 loss-of-function (constitutive and conditional KO) blunts hypothalamic glucose detection, food intake regulation, and glucose-stimulated insulin secretion. Constitutive and conditional TRPC3 KO mice, in vitro Ca2+ imaging of MBH neurons, intracerebroventricular glucose injection, intracarotid glucose injection, food intake measurement Diabetes High 27899482
2009 NO inhibits TRPC3 (in complex with TRPC1) via a PKG-dependent mechanism in vascular smooth muscle cells; NO/cGMP/PKG inhibition of TRPC1/TRPC3 channels contributes to vasorelaxation. Whole-cell patch clamp in freshly isolated SMC, intracellular antibody blockade, co-immunoprecipitation of TRPC1 with TRPC3, PKG inhibitor (KT5823), vessel myograph American journal of physiology. Heart and circulatory physiology High 19502552
2012 TRPC3 mediates IgG immune complex-induced non-selective cation current in rat DRG neurons through the Syk-PLC-IP3 signaling pathway downstream of Fcγ receptor I; selective TRPC3 siRNA knockdown attenuates the IgG-IC-induced Ca2+ response. Whole-cell patch clamp, siRNA knockdown of TRPC3, Syk inhibitor, PLC inhibitor, IP3R antagonists, single-cell RT-PCR The Journal of neuroscience High 22787041
2021 METTL3 stabilizes TRPC3 mRNA via m6A modification; PLAA inhibits METTL3 expression through ubiquitin-mediated degradation, reducing TRPC3-mediated Ca2+ influx and suppressing ovarian cancer metastasis. Ubiquitination assay, m6A methylation analysis, TRPC3 mRNA stability assay, Ca2+ influx measurements, orthotopic xenograft model Oncogene Medium 35869392
2021 Progesterone receptor isoform B (PGR-B) suppresses uterine contractility by reducing Trpc3 and Oxtr expression and increasing Plcl2, compromising oxytocin-TRPC3 signaling; PGR-B overexpression in smooth muscle prolongs gestational length in mice. Transgenic mouse models overexpressing PGR-A or PGR-B in smooth muscle, RNA-seq, CRISPRa functional assay, contractility measurements Proceedings of the National Academy of Sciences of the United States of America Medium 33707208
2018 TRPC3 and TRPC7 form heteromeric channels activated by P2Y2 receptor stimulation with ATP/UTP via G protein and PLCβ in ventricular cardiomyocytes; anti-TRPC3 intracellular antibody inhibits the current and TRPC3/TRPC7 co-immunoprecipitate from native cardiac tissue. Whole-cell patch clamp with intracellular anti-TRPC3 antibody, co-immunoprecipitation from rat ventricular myocytes, Mn2+ quench, Ba2+ influx American journal of physiology. Heart and circulatory physiology High 18502908
2017 TRPC3 mediates Na+ influx downstream of DAG/PLCγ activation by VEGF, which drives reverse-mode NCX operation, ERK1/2 activation, and endothelial tubular differentiation (angiogenesis); TRPC3 and NCX are functionally coupled in this pathway. TRPC3 siRNA, TRPC3 inhibitors, reverse-mode NCX inhibitors, Na+ influx assay, ERK1/2 phosphorylation, tubulogenesis assay in human endothelial cells Cellular signalling Medium 28535874
2017 TRPC3 and TRPC6 contribute to the physiological stretch-induced slow force response (SFR) in cardiomyocytes by mediating stretch-induced intracellular Ca2+ increases that activate calcineurin/NFAT; under pathological chronic stress, TRPC3/TRPC6 mediate hypertrophic signaling. Mechanical stretch protocols in cardiomyocytes, TRPC3/6 inhibitors, Ca2+ imaging (review citing original experimental data) Progress in biophysics and molecular biology Medium 28645743
2015 Combined genetic deletion of TRPC3 and TRPC6 protects mice from pressure overload-induced cardiac hypertrophy and dysfunction, whereas single deletion of either channel alone is insufficient, demonstrating functional redundancy and the need for dual inhibition. Single and double TRPC3/TRPC6 KO mice, transverse aortic constriction, echocardiography, histology Proceedings of the National Academy of Sciences of the United States of America High 24453217
2010 TRPC3 constitutive function in human coronary artery endothelial cells is required for proper NF-κB activation and VCAM-1 expression; TRPC3 knockdown reduces TNFα-induced IκBα phosphorylation/degradation and VCAM-1 expression; the mechanism requires calmodulin-dependent signaling downstream of constitutive TRPC3-mediated Ca2+ influx. TRPC3 siRNA, TRPC3 overexpression in HEK293 and HCAEC, NF-κB pathway analysis, calmodulin inhibition, monocyte adhesion assay Circulation research Medium 20360250
2012 TRPC3 interacts with TRPC1 in cortical astrocytes to form heteromeric channels where TRPC1 reduces TRPC3 activity; TRPC3 is required for astrocyte Ca2+ entry, proliferation, and migration in vitro and for astrogliosis following brain injury in vivo. Co-immunoprecipitation of TRPC1/TRPC3 in HEK-293, TRPC3 KO and TRPC1 KO mice, stab wound injury model, astrocyte Ca2+ imaging, migration and proliferation assays Glia High 28636132
2012 STIM1L (splice variant of STIM1) binds more abundantly to TRPC3 than canonical STIM1, and tends to suppress TRPC3/TRPC6-mediated receptor-operated Ca2+ entry more strongly; co-immunoprecipitation confirms differential STIM1/STIM1L binding to TRPC3. Co-immunoprecipitation, Ca2+ influx measurements in HEK293 cells stably expressing ETA receptor Biochemical and biophysical research communications Medium 23068106
2009 A pathogenic C-terminal truncated polycystin-2 (TRPP2) mutant (697fsX) physically associates with TRPC3 at the plasma membrane, altering ion-permeating pore properties and enhancing receptor-activated Ca2+ influx; wild-type TRPP2 is ER-localized and does not associate with TRPC3. Co-immunoprecipitation, pull-down assay, cross-linking, single-channel recording, confocal microscopy in HEK293 and LLC-PK1 cells The Journal of biological chemistry Medium 19812035

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature 1273 9930701
2009 Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound. Proceedings of the National Academy of Sciences of the United States of America 313 19289841
1999 Activation of a TRPC3-dependent cation current through the neurotrophin BDNF. Neuron 287 10677043
2002 Comparison of human TRPC3 channels in receptor-activated and store-operated modes. Differential sensitivity to channel blockers suggests fundamental differences in channel composition. The Journal of biological chemistry 212 11943785
2005 Endogenous TRPC1, TRPC3, and TRPC7 proteins combine to form native store-operated channels in HEK-293 cells. The Journal of biological chemistry 172 15972814
2003 N-linked protein glycosylation is a major determinant for basal TRPC3 and TRPC6 channel activity. The Journal of biological chemistry 166 12970363
2014 Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy. Proceedings of the National Academy of Sciences of the United States of America 165 24453217
2005 Phospholipase Cgamma1 controls surface expression of TRPC3 through an intermolecular PH domain. Nature 156 15744307
2018 Structure of the receptor-activated human TRPC6 and TRPC3 ion channels. Cell research 152 29700422
2003 Signaling mechanism for receptor-activated canonical transient receptor potential 3 (TRPC3) channels. The Journal of biological chemistry 139 12606542
2012 TRPC3 and TRPC6 are essential for normal mechanotransduction in subsets of sensory neurons and cochlear hair cells. Open biology 134 22724068
2004 TRPC3 mediates pyrimidine receptor-induced depolarization of cerebral arteries. American journal of physiology. Heart and circulatory physiology 129 15604128
2005 The diacylgylcerol-sensitive TRPC3/6/7 subfamily of cation channels: functional characterization and physiological relevance. Pflugers Archiv : European journal of physiology 126 15971081
2004 Obligatory role of Src kinase in the signaling mechanism for TRPC3 cation channels. The Journal of biological chemistry 123 15271991
2003 TRPC3 mediates T-cell receptor-dependent calcium entry in human T-lymphocytes. The Journal of biological chemistry 109 12736256
2004 Negative regulation of TRPC3 channels by protein kinase C-mediated phosphorylation of serine 712. Molecular pharmacology 107 15533987
2017 Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling. Nature communications 102 28181498
2007 Complex regulation of the TRPC3, 6 and 7 channel subfamily by diacylglycerol and phosphatidylinositol-4,5-bisphosphate. Cell calcium 100 17942152
2011 Genetic and pharmacologic inhibition of the Ca2+ influx channel TRPC3 protects secretory epithelia from Ca2+-dependent toxicity. Gastroenterology 99 21354153
2008 Store-operated Ca2+ channels formed by TRPC1, TRPC6 and Orai1 and non-store-operated channels formed by TRPC3 are involved in the regulation of NADPH oxidase in HL-60 granulocytes. Cell calcium 98 18436303
2008 IP3 constricts cerebral arteries via IP3 receptor-mediated TRPC3 channel activation and independently of sarcoplasmic reticulum Ca2+ release. Circulation research 93 18388325
2008 Canonical transient receptor potential channel (TRPC)3 and TRPC6 associate with large-conductance Ca2+-activated K+ (BKCa) channels: role in BKCa trafficking to the surface of cultured podocytes. Molecular pharmacology 93 19052171
2005 Receptor-operated Ca2+ entry mediated by TRPC3/TRPC6 proteins in rat prostate smooth muscle (PS1) cell line. Journal of cellular physiology 92 15672411
2011 TRP expression pattern and the functional importance of TRPC3 in primary human T-cells. Biochimica et biophysica acta 89 21215279
2011 Pharmacological modulation of diacylglycerol-sensitive TRPC3/6/7 channels. Current pharmaceutical biotechnology 86 20932261
2005 Functional characterization and physiological relevance of the TRPC3/6/7 subfamily of cation channels. Naunyn-Schmiedeberg's archives of pharmacology 81 15909153
2006 Functional coupling between TRPC3 and RyR1 regulates the expressions of key triadic proteins. The Journal of biological chemistry 79 16484216
2006 Phospholipase C-dependent control of cardiac calcium homeostasis involves a TRPC3-NCX1 signaling complex. Cardiovascular research 76 17129578
2015 TRPC3 contributes to regulation of cardiac contractility and arrhythmogenesis by dynamic interaction with NCX1. Cardiovascular research 73 25631581
2003 A calmodulin/inositol 1,4,5-trisphosphate (IP3) receptor-binding region targets TRPC3 to the plasma membrane in a calmodulin/IP3 receptor-independent process. The Journal of biological chemistry 73 12730194
2009 TRPC3 regulates agonist-stimulated Ca2+ mobilization by mediating the interaction between type I inositol 1,4,5-trisphosphate receptor, RACK1, and Orai1. The Journal of biological chemistry 67 20022948
2009 Inhibition of TRPC1/TRPC3 by PKG contributes to NO-mediated vasorelaxation. American journal of physiology. Heart and circulatory physiology 64 19502552
2007 TrpC3/C7 and Slo2.1 are molecular targets for metabotropic glutamate receptor signaling in rat striatal cholinergic interneurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 64 17699666
2015 Brain-derived neurotrophic factor regulates TRPC3/6 channels and protects against myocardial infarction in rodents. International journal of biological sciences 63 25892961
2018 LncRNA SNHG5 promotes growth and invasion in melanoma by regulating the miR-26a-5p/TRPC3 pathway. OncoTargets and therapy 61 30636880
2005 Increased transient receptor potential channel TRPC3 expression in spontaneously hypertensive rats. American journal of hypertension 61 16280289
2010 The constitutive function of native TRPC3 channels modulates vascular cell adhesion molecule-1 expression in coronary endothelial cells through nuclear factor kappaB signaling. Circulation research 60 20360250
2012 Transient receptor potential canonical 3 (TRPC3) is required for IgG immune complex-induced excitation of the rat dorsal root ganglion neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 59 22787041
2022 TRPC3 shapes the ER-mitochondria Ca2+ transfer characterizing tumour-promoting senescence. Nature communications 57 35177596
2014 TRPC3 channels critically regulate hippocampal excitability and contextual fear memory. Behavioural brain research 54 25513972
2017 Role of TRPC3 and TRPC6 channels in the myocardial response to stretch: Linking physiology and pathophysiology. Progress in biophysics and molecular biology 53 28645743
2014 Contribution of TRPC3 to store-operated calcium entry and inflammatory transductions in primary nociceptors. Molecular pain 50 24965271
2011 mGluR1/TRPC3-mediated Synaptic Transmission and Calcium Signaling in Mammalian Central Neurons. Cold Spring Harbor perspectives in biology 49 21441586
2006 TRPC3 channels colocalize with Na+/Ca2+ exchanger and Na+ pump in axial component of transverse-axial tubular system of rat ventricle. American journal of physiology. Heart and circulatory physiology 49 17012351
2018 miR-26a inhibits atherosclerosis progression by targeting TRPC3. Cell & bioscience 48 29387339
2010 Activation of the neurokinin-1 receptor in rat spinal astrocytes induces Ca2+ release from IP3-sensitive Ca2+ stores and extracellular Ca2+ influx through TRPC3. Neurochemistry international 46 20933035
2006 Cellular cholesterol controls TRPC3 function: evidence from a novel dominant-negative knockdown strategy. The Biochemical journal 45 16448384
2013 The discovery of potent blockers of the canonical transient receptor channels, TRPC3 and TRPC6, based on an anilino-thiazole pharmacophore. Bioorganic & medicinal chemistry letters 44 23886683
2011 TRPC3 channel contributes to nitric oxide release: significance during normoxia and hypoxia-reoxygenation. Cardiovascular research 42 21493700
2009 Enhanced expression of STIM1/Orai1 and TRPC3 in platelets from patients with type 2 diabetes mellitus. Blood cells, molecules & diseases 42 19447651
2008 TRPC3 controls agonist-stimulated intracellular Ca2+ release by mediating the interaction between inositol 1,4,5-trisphosphate receptor and RACK1. The Journal of biological chemistry 42 18755685
2008 Involvement of native TRPC3 proteins in ATP-dependent expression of VCAM-1 and monocyte adherence in coronary artery endothelial cells. Arteriosclerosis, thrombosis, and vascular biology 42 18787184
2017 Coupling between the TRPC3 ion channel and the NCX1 transporter contributed to VEGF-induced ERK1/2 activation and angiogenesis in human primary endothelial cells. Cellular signalling 41 28535874
2016 Differences in TRPC3 and TRPC6 channels assembly in mesenteric vascular smooth muscle cells in essential hypertension. The Journal of physiology 41 27861908
2019 Trimetazidine prevents diabetic cardiomyopathy by inhibiting Nox2/TRPC3-induced oxidative stress. Journal of pharmacological sciences 39 30962089
2015 Proarrhythmic effect of sustained EPAC activation on TRPC3/4 in rat ventricular cardiomyocytes. Journal of molecular and cellular cardiology 39 26219954
2014 Calcium sensing receptor modulates extracellular calcium entry and proliferation via TRPC3/6 channels in cultured human mesangial cells. PloS one 39 24905090
2012 Different binding property of STIM1 and its novel splice variant STIM1L to Orai1, TRPC3, and TRPC6 channels. Biochemical and biophysical research communications 39 23068106
2011 Serine-threonine kinase with-no-lysine 4 (WNK4) controls blood pressure via transient receptor potential canonical 3 (TRPC3) in the vasculature. Proceedings of the National Academy of Sciences of the United States of America 38 21670282
2017 TRPC3 Channels in Cardiac Fibrosis. Frontiers in cardiovascular medicine 37 28936433
2012 Role of TRPC1 and TRPC3 channels in contraction and relaxation of mouse thoracic aorta. Journal of vascular research 37 23095462
2015 Hypertrophic scar contracture is mediated by the TRPC3 mechanical force transducer via NFkB activation. Scientific reports 35 26108359
2013 The histone variant MacroH2A regulates Ca(2+) influx through TRPC3 and TRPC6 channels. Oncogenesis 35 24165580
2019 Lipid-independent control of endothelial and neuronal TRPC3 channels by light. Chemical science 34 30997005
2008 TRPM4b channel suppresses store-operated Ca2+ entry by a novel protein-protein interaction with the TRPC3 channel. Biochemical and biophysical research communications 34 18262493
2014 The Moonwalker mouse: new insights into TRPC3 function, cerebellar development, and ataxia. Cerebellum (London, England) 33 24797279
2014 Activation of calcium-sensing receptor increases TRPC3/6 expression in T lymphocyte in sepsis. Molecular immunology 33 25467798
2012 Effect of oxidative stress on TRPM2 and TRPC3 channels in B lymphoblast cells in bipolar disorder. Bipolar disorders 33 22420591
2017 TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice. Scientific reports 32 28790356
2011 Impairment of survival signaling and efferocytosis in TRPC3-deficient macrophages. Biochemical and biophysical research communications 32 21684255
2008 ATP/UTP activate cation-permeable channels with TRPC3/7 properties in rat cardiomyocytes. American journal of physiology. Heart and circulatory physiology 32 18502908
2022 PLAA suppresses ovarian cancer metastasis via METTL3-mediated m6A modification of TRPC3 mRNA. Oncogene 31 35869392
2017 Treatment with TREK1 and TRPC3/6 ion channel inhibitors upregulates microRNA expression in a mouse model of chronic mild stress. Neuroscience letters 31 28716528
2011 Upregulated TRPC3 and Downregulated TRPC1 Channel Expression during Hypertension is Associated with Increased Vascular Contractility in Rat. Frontiers in physiology 31 21811471
2021 TRPC3 promotes tumorigenesis of gastric cancer via the CNB2/GSK3β/NFATc2 signaling pathway. Cancer letters 30 34311033
2019 Protective mechanism of SIRT1 on Hcy-induced atrial fibrosis mediated by TRPC3. Journal of cellular and molecular medicine 30 31680473
2022 Mesenchymal stem cells derived from adipose accelerate the progression of colon cancer by inducing a MT-CAFs phenotype via TRPC3/NF-KB axis. Stem cell research & therapy 29 35870973
2018 HERV-W env regulates calcium influx via activating TRPC3 channel together with depressing DISC1 in human neuroblastoma cells. Journal of neurovirology 29 30397826
2015 The contribution of TRPC1, TRPC3, TRPC5 and TRPC6 to touch and hearing. Neuroscience letters 29 26520460
2014 Reduced endoplasmic reticulum stress-induced apoptosis and impaired unfolded protein response in TRPC3-deficient M1 macrophages. American journal of physiology. Cell physiology 29 25031020
2021 Progesterone receptor isoform B regulates the Oxtr-Plcl2-Trpc3 pathway to suppress uterine contractility. Proceedings of the National Academy of Sciences of the United States of America 28 33707208
2019 Ibudilast attenuates doxorubicin-induced cytotoxicity by suppressing formation of TRPC3 channel and NADPH oxidase 2 protein complexes. British journal of pharmacology 28 31241172
2018 Transient Receptor Potential Channels TRPM4 and TRPC3 Critically Contribute to Respiratory Motor Pattern Formation but not Rhythmogenesis in Rodent Brainstem Circuits. eNeuro 28 29435486
2016 Transient Receptor Potential Canonical 3 (TRPC3) Channels Are Required for Hypothalamic Glucose Detection and Energy Homeostasis. Diabetes 28 27899482
2009 A pathogenic C terminus-truncated polycystin-2 mutant enhances receptor-activated Ca2+ entry via association with TRPC3 and TRPC7. The Journal of biological chemistry 27 19812035
2017 TRPC1- and TRPC3-dependent Ca2+ signaling in mouse cortical astrocytes affects injury-evoked astrogliosis in vivo. Glia 26 28636132
2015 The mutant Moonwalker TRPC3 channel links calcium signaling to lipid metabolism in the developing cerebellum. Human molecular genetics 26 25908616
2012 On the role of endothelial TRPC3 channels in endothelial dysfunction and cardiovascular disease. Cardiovascular & hematological agents in medicinal chemistry 24 22827251
2010 Role of TRPC3 channels in ATP-induced Ca2+ signaling in principal cells of the inner medullary collecting duct. American journal of physiology. Renal physiology 24 20410214
2014 Adaptive responses of TRPC1 and TRPC3 during skeletal muscle atrophy and regrowth. Muscle & nerve 23 23852583
2022 Inhibition of TRPC3 channels by a novel pyrazole compound confers antiseizure effects. Epilepsia 22 35179226
2015 TRPC3 regulates the automaticity of embryonic stem cell-derived cardiomyocytes. International journal of cardiology 22 26512833
2012 Role of TRPC3 channel in human internal mammary artery. Archives of medical research 22 22960861
2010 TRPC3 cation channel plays an important role in proliferation and differentiation of skeletal muscle myoblasts. Experimental & molecular medicine 22 20644344
2007 Suppression of TRPC3 leads to disappearance of store-operated channels and formation of a new type of store-independent channels in A431 cells. The Journal of biological chemistry 22 17569672
2022 Diacylglycerols interact with the L2 lipidation site in TRPC3 to induce a sensitized channel state. EMBO reports 21 35604352
2020 lncRNA DLX6-AS1 Promotes Proliferation of Laryngeal Cancer Cells by Targeting the miR-26a/TRPC3 Pathway. Cancer management and research 21 32368147
2015 The involvement of TRPC3 channels in sinoatrial arrhythmias. Frontiers in physiology 21 25859221
2017 TRPC3- and ETB receptor-mediated PI3K/AKT activation induces vasogenic edema formation following status epilepticus. Brain research 20 28764936
2010 Developmental regulation of TRPC3 ion channel expression in the mouse cochlea. Histochemistry and cell biology 19 20229053