Affinage

TRPC5

Short transient receptor potential channel 5 · UniProt Q9UL62

Length
973 aa
Mass
111.4 kDa
Annotated
2026-06-10
100 papers in source corpus 50 papers cited in narrative 50 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRPC5 is a Ca2+-permeable, nonselective cation channel that couples Gq/11- and Gi-coupled receptor signaling and diverse physicochemical stimuli to localized Ca2+ entry, thereby controlling neuronal excitability, cytoskeletal dynamics, and cell migration (PMID:10837492, PMID:19450521, PMID:20978238). It functions as a receptor-operated channel activated downstream of Gq/11 receptors and receptor tyrosine kinases independently of store depletion (PMID:10837492), with Gαi subunits (predominantly Gαi3) serving as direct activators that bind the channel and, as resolved by cryo-EM of the 4:4 TRPC5–Gαi3 complex, dock on the ankyrin-repeat edge ~50 Å from the membrane to increase channel sensitivity to PIP2 (PMID:37137991, PMID:22457348). The channel assembles as homotetramers or as heteromultimers selectively with TRPC1 and TRPC4 (PMID:11301024, PMID:28790178), an assembly that gates which stimuli are sensed—homomeric TRPC5 is cold-sensitive whereas TRPC1/TRPC5 heteromers are not (PMID:22025699). N-terminal ankyrin repeats drive multimerization (PMID:17624425) and extracellular pore-loop disulfide bonds (Cys553/Cys558) are required for tetramerization, trafficking, and activity (PMID:24859801), consistent with the disulfide-bonded extracellular pore resolved in the 2.8 Å homotetramer structure (PMID:31355338). TRPC5 integrates a remarkable breadth of gating inputs: intracellular Ca2+ potentiation (PMID:19398778, PMID:19815560), lysophospholipids (PMID:16368680), membrane stretch and hypoosmolarity (PMID:18832422), extracellular protons and lanthanides acting at pore glutamates E543/E595 (PMID:12456670, PMID:17884814), bidirectional PIP2 regulation (PMID:18665391, PMID:33933453), oxidative S-glutathionylation at Cys176/Cys178 (PMID:26133660), and proteolytic activation by calpain at Thr857 (PMID:22547824). Its activity is tuned by C-terminal binding partners—calmodulin and the CIRB domain (PMID:15987684), CaBP1 and NCS-1 (PMID:16469785, PMID:15895247), SESTD1 (PMID:20164195), and the PDZ scaffold EBP50 (PMID:15334657)—and is inhibited by PKA phosphorylation at Ser794/Ser796 (PMID:21734191). Functionally, TRPC5-mediated Ca2+ influx restrains neurite and dendrite growth, signaling through stathmin 2, CaMKIIβ–Cdc20-APC, and NT-3/TrkC pathways (PMID:12858178, PMID:22135323, PMID:22764246), and in podocytes it complexes with and activates Rac1 to drive cytoskeletal remodeling and filtration-barrier injury (PMID:20978238, PMID:24231357). In the brain, TRPC5 is required for innate fear, hippocampal LTP and working memory, seizure susceptibility, and POMC-neuron responses to leptin, serotonin, and insulin governing energy homeostasis (PMID:19450521, PMID:23188715, PMID:28790178, PMID:28099839, PMID:28675783). In cancer, TRPC5 drives NFATc3-dependent P-glycoprotein induction and cytoprotective autophagy underlying chemoresistance, and is propagated between cells via extracellular vesicles (PMID:22988121, PMID:28600513, PMID:24733904).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 High

    Established TRPC5 as a receptor-operated rather than store-operated channel, defining its core signaling logic.

    Evidence Whole-cell and inside-out patch-clamp with Mn2+ quench in HEK293 cells expressing mTRPC5

    PMID:10837492

    Open questions at the time
    • Did not resolve the direct molecular link from Gq/11 to the channel
    • Single-channel gating mechanism left open
  2. 2001 High

    Showed TRPC5 does not act alone but co-assembles with TRPC1 into a native neuronal heteromeric channel, raising the question of subunit-defined channel diversity.

    Evidence Reciprocal Co-IP from brain plus heterologous coexpression electrophysiology in HEK293 cells

    PMID:11301024

    Open questions at the time
    • Stoichiometry of heteromers undefined
    • Functional distinction of homo vs heteromers not yet established
  3. 2003 High

    Defined a cell-biological role: TRPC5 traffics to growth cones and restrains neurite extension, linking channel activity to neuronal morphogenesis.

    Evidence Co-IP with stathmin 2, dominant-negative expression, and live imaging in rat hippocampal neurons

    PMID:12858178

    Open questions at the time
    • Mechanism by which stathmin 2 couples to channel function unclear
    • Downstream cytoskeletal effectors not fully mapped
  4. 2005 High

    Identified multiple C-terminal Ca2+-sensor and lipid-binding partners (CaM/CIRB, CaBP1, SESTD1 later) and lysophospholipid sensitivity, framing TRPC5 as a polymodal, tightly regulated channel.

    Evidence Mutagenesis, in vitro binding/pull-down, and patch-clamp across CHO/HEK293/Xenopus systems; excised-patch lysophospholipid activation

    PMID:15895247 PMID:15987684 PMID:16368680

    Open questions at the time
    • How competing Ca2+ sensors are coordinated in cells unresolved
    • Direct vs membrane-mediated lysophospholipid action not definitively separated
  5. 2008 High

    Established mechanosensitivity and bidirectional PIP2 regulation, expanding the polymodal gating repertoire and revealing context-dependent lipid control.

    Evidence Excised-patch and whole-cell patch-clamp with pressure application, PIP2 depletion/infusion in HEK293 cells

    PMID:18665391 PMID:18832422

    Open questions at the time
    • Molecular site of mechanical sensing unidentified
    • Reconciling stimulatory vs inhibitory PIP2 effects mechanistically incomplete
  6. 2009 High

    Demonstrated an essential in vivo role in innate fear circuits and quantified intracellular Ca2+ potentiation, connecting molecular gating to behavior.

    Evidence TRPC5 KO mice with amygdala electrophysiology and fear behavior; caged-Ca2+ single-channel recordings

    PMID:19398778 PMID:19450521 PMID:19815560

    Open questions at the time
    • Identity of the intracellular Ca2+ binding site not resolved
    • Receptor specificity in vivo only partially mapped
  7. 2010 High

    Placed TRPC5 in opposition to TRPC6 as an antagonistic regulator of actin dynamics via direct complex with Rac1, providing a migration-control mechanism.

    Evidence Reciprocal Co-IP, siRNA, migration and Ca2+ imaging in podocytes and fibroblasts

    PMID:20978238

    Open questions at the time
    • How Ca2+ influx selectively activates Rac1 vs RhoA unclear
    • Structural basis of TRPC5-Rac1 complex unknown
  8. 2011 High

    Linked TRPC5 Ca2+ signaling to a specific dendrite-patterning pathway and to cold sensing, refining its developmental and sensory roles.

    Evidence KO mice, in vivo RNAi, Co-IP of TRPC5–CaMKIIβ; temperature-evoked electrophysiology of homo vs heteromers

    PMID:22025699 PMID:22135323

    Open questions at the time
    • How channel activity is converted to centrosomal Cdc20-APC phosphorylation incompletely defined
    • Molecular determinant of cold sensing in TRPC5 unmapped
  9. 2012 High

    Revealed proteolytic activation by calpain and direct Gαi activation via the SESTD domain, and extended pathophysiology to seizures, drug resistance, and neurotrophin signaling.

    Evidence In vitro calpain cleavage with T857 mutagenesis; Co-IP and constitutively active Gαi electrophysiology; KO seizure models; NFAT reporter and xenograft assays; NT-3/TrkC dissection in neurons

    PMID:22457348 PMID:22547824 PMID:22764246 PMID:22988121 PMID:23188715

    Open questions at the time
    • Physiological triggers of calpain cleavage in vivo unclear
    • How distinct activators converge on gating not unified
  10. 2013 High

    Identified gating elements (S4-S5 linker Gly504) and an in vivo role in kidney filtration-barrier injury, connecting channel conformation to disease.

    Evidence G504S and suppressor mutagenesis with cell-death assays; Trpc5-KO mice and inhibitor with podocyte imaging and albuminuria

    PMID:23677990 PMID:24231357

    Open questions at the time
    • Full open-state conformational pathway not resolved without structure at the time
    • Endogenous activator driving podocyte injury not pinpointed
  11. 2014 High

    Defined pore-loop disulfide bonds essential for assembly/trafficking and demonstrated intercellular spread of resistance via TRPC5-bearing extracellular vesicles.

    Evidence Cys553/Cys558 mutagenesis with FRET, Co-IP, surface biotinylation; EV isolation/transfer with NFATc3-P-gp readouts and xenografts

    PMID:24733904 PMID:24859801

    Open questions at the time
    • EV transfer mechanism and in vivo relevance only partly characterized
    • Link between disulfide redox state and physiological gating incomplete
  12. 2015 High

    Showed oxidative S-glutathionylation at Cys176/Cys178 activates TRPC5 to drive striatal neuronal death, implicating the channel in Huntington's disease pathology.

    Evidence Cysteine mutagenesis glutathionylation assay, electrophysiology, KO/inhibition, YAC128 mice and human HD tissue

    PMID:26133660

    Open questions at the time
    • Whether HD-relevant activation is reversible therapeutically untested here
    • Interplay with TRPC1 expression in determining homotetramer fraction only correlative
  13. 2017 High

    Used native complexomics and triple-KO mice to define a TRPC1/4/5 channel family and established TRPC5 roles in synaptic transmission, working memory, and POMC energy homeostasis.

    Evidence Quantitative MS of native complexes, Trpc1/4/5 triple-KO with electrophysiology and memory tasks; POMC-conditional Trpc5 KO with metabolic phenotyping

    PMID:28099839 PMID:28600513 PMID:28790178

    Open questions at the time
    • Subunit composition of physiologically relevant channels in each tissue still uncertain
    • Autophagy pathway link (Medium confidence) needs broader validation
  14. 2019 High

    Solved the homotetramer cryo-EM structure and revealed palmitoylation and additional neuroendocrine functions, providing a structural and post-translational framework.

    Evidence 2.8 Å cryo-EM with mutagenesis; palmitoylation assay in HD striatal cells; conditional KO with prolactin/reproductive phenotyping

    PMID:31285329 PMID:31355338 PMID:31812495

    Open questions at the time
    • Ligand- and state-specific conformations not captured
    • Palmitoylation enzyme/site identity (Medium confidence) not fully defined
  15. 2023 High

    Resolved the TRPC5–Gαi3 complex structure, defining how a direct G-protein interaction at the ankyrin domain potentiates PIP2 sensitivity to open the channel.

    Evidence Cryo-EM in lipid nanodiscs with PIP2-sensitivity electrophysiology

    PMID:37137991

    Open questions at the time
    • Conformational transitions linking Gαi3 binding to pore opening not fully traced
    • Generalizability to heteromeric channels untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the channel's many gating modalities, subunit compositions, and tissue-specific partners are integrated to produce distinct physiological Ca2+ signals remains unresolved.
  • No unified model linking polymodal stimuli to defined open states across cell types
  • Tissue-specific heteromer stoichiometry and partner dependence incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0140299 molecular sensor activity 4 GO:0060089 molecular transducer activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005856 cytoskeleton 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-112316 Neuronal System 5 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3
Partners
CABP1CAMK2BGNAI3NCS1RAC1SESTD1TRPC1TRPC4
Complex memberships
TRPC1/TRPC4/TRPC5 heteromeric channelTRPC5–CaMKIIβ complexTRPC5–Gαi3 complexTRPC5–Rac1 complex

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 TRPC1 and TRPC5 co-assemble into a heteromeric neuronal cation channel in the hippocampus. Coexpression in HEK293 cells produced a novel nonselective cation channel with voltage dependence similar to NMDA receptors, activated by Gq-coupled receptors but not by intracellular Ca2+ store depletion. Co-immunoprecipitation, heterologous coexpression in HEK293 cells, whole-cell patch-clamp electrophysiology Neuron High 11301024
2000 TRPC5 (mTRPC5) forms a receptor-operated nonselective cation channel (single-channel conductance ~66 pS at -60 mV) activated by Gq/11-coupled receptors and receptor tyrosine kinases independently of intracellular Ca2+ store depletion; GTPγS activates channels in inside-out patches in a membrane-confined manner. Whole-cell patch-clamp, inside-out patch recording, Mn2+ quench assay in fura-2-loaded HEK293 cells The Journal of biological chemistry High 10837492
2003 TRPC5 is expressed in neuronal growth cones, interacts with the growth cone-enriched protein stathmin 2, is packaged into vesicles and transported to growth cones and synapses. TRPC5 channel activity restrains neurite extension and growth cone morphology, as dominant-negative TRPC5 expression allowed significantly longer neurites and filopodia. Co-immunoprecipitation (TRPC5-stathmin 2 interaction), dominant-negative expression, live-cell imaging, immunofluorescence in rat hippocampal neurons Nature neuroscience High 12858178
2002 Lanthanide ions (La3+, Gd3+) potentiate TRPC5 currents at micromolar concentrations via extracellular sites near the pore mouth. Neutralization of negatively charged residues Glu543 and Glu595/Glu598 abolished potentiation; these residues are accessible from the extracellular side. The mechanism involves reduced single-channel conductance but dramatic increase in open probability. Site-directed mutagenesis, whole-cell and outside-out patch-clamp recordings in HEK293 cells The Journal of biological chemistry High 12456670
2009 TRPC5-/- mice exhibit diminished innate fear and reduced responses mediated by Group I metabotropic glutamate and CCK2 receptors in amygdala neurons, demonstrating that TRPC5, activated via G protein-coupled neuronal receptors, has an essential function in innate fear circuits. TRPC5 knockout mice, electrophysiology in amygdala slices, behavioral fear assays Cell High 19450521
2010 TRPC5 forms a molecular complex with Rac1 in podocytes and fibroblasts; TRPC5-mediated Ca2+ influx activates Rac1, promoting cell migration. Conversely, TRPC6 is in complex with RhoA and its Ca2+ influx activates RhoA to inhibit migration, establishing TRPC5 and TRPC6 as antagonistic regulators of actin dynamics. Co-immunoprecipitation (TRPC5-Rac1 and TRPC6-RhoA complexes), siRNA knockdown, cell migration assays, Ca2+ imaging in podocytes and fibroblasts Science signaling High 20978238
2013 TRPC5 mediates kidney filtration barrier injury. Loss of TRPC5 (Trpc5-KO mice) or pharmacological inhibition prevents podocyte cytoskeletal remodeling, blocks Rac1 activation, stabilizes synaptopodin, and protects against albuminuria. Trpc5 knockout mice, small-molecule TRPC5 inhibitor, Ca2+ imaging in isolated glomeruli, live imaging of podocyte actin dynamics, urine albumin measurement The Journal of clinical investigation High 24231357
2012 TRPC5 activity drives P-glycoprotein (P-gp) induction in adriamycin-resistant breast cancer cells via an NFATc3-dependent transcriptional mechanism (TRPC5-NFATc3-P-gp signaling cascade). Suppression of TRPC5 reduced P-gp expression and reversed drug resistance in vitro and in a xenograft model. siRNA knockdown, channel inhibition, NFAT reporter assay, Western blotting, xenograft tumor model Proceedings of the National Academy of Sciences of the United States of America High 22988121
2011 TRPC5 is activated by cold temperatures in the range 37–25°C. Homomeric TRPC5 channels, but not TRPC1/TRPC5 heteromeric channels, are cold-sensitive. TRPC5 is present in dorsal root ganglion sensory neurons and peripheral nerve endings consistent with a role as an innocuous cold transducer. Temperature-evoked electrophysiology (cold activation of expressed TRPC5), TRPC5 KO mice behavioral testing, immunohistochemistry of DRG neurons Proceedings of the National Academy of Sciences of the United States of America High 22025699
2009 Intracellular Ca2+ potentiates TRPC5 channel activity: ~1 µM intracellular Ca2+ triggers ~10–20-fold increase in channel open probability in excised inside-out patches without changing single-channel conductance. Extracellular Ca2+ (not Ba2+ or Mg2+) is required for the potentiation, acting at an intracellular site. Simultaneous fura-2 imaging and patch-clamp, excised inside-out single-channel recordings, caged Ca2+ photolysis, whole-cell patch-clamp in HEK293 cells The Journal of general physiology High 19398778
2012 Calpain-1 and calpain-2 cleave and functionally activate TRPC5. A critical threonine at position 857 is required for calpain-2 cleavage. The truncated TRPC5 resulting from calpain cleavage is functionally active. This mechanism mediates semaphorin 3A-induced growth cone collapse in hippocampal neurons. In vitro calpain cleavage assay, site-directed mutagenesis (T857 mutant), TRPC5-null hippocampal neurons, electrophysiology, growth cone collapse assay Proceedings of the National Academy of Sciences of the United States of America High 22547824
2011 TRPC5 KO mice have long, highly branched cerebellar granule neuron dendrites with impaired dendritic claw differentiation. TRPC5 forms a complex specifically with CaMKIIβ (not CaMKIIα) and induces CaMKIIβ-dependent phosphorylation of the ubiquitin ligase Cdc20-APC at the centrosome, coupling Ca2+ signaling to a ubiquitin ligase pathway to regulate dendrite patterning. TRPC5 KO mice, in vivo RNAi, Co-immunoprecipitation (TRPC5-CaMKIIβ complex), phosphorylation assays, behavioral motor coordination tests Genes & development High 22135323
2012 TRPC5 KO mice show significantly reduced pilocarpine-induced seizures and minimal seizure-induced hippocampal neuronal death, whereas TRPC1/4 double KO mice show unaltered seizures but reduce epileptiform bursting in lateral septal neurons—demonstrating that TRPC5 and TRPC1/4 contribute to seizures and excitotoxicity via distinct cellular mechanisms. Long-term potentiation is greatly reduced in TRPC5 KO hippocampi. TRPC5 KO mice, TRPC1 KO mice, TRPC1/4 double-KO mice, pilocarpine seizure model, hippocampal slice electrophysiology, LTP recordings Molecular pharmacology High 23188715
2015 TRPC5 glutathionylation at Cys176/Cys178 by intracellular oxidized glutathione activates TRPC5 channels, causing sustained Ca2+ influx, calmodulin-dependent protein kinase activation, and calpain-caspase-mediated striatal neuronal death. Increased TRPC5 S-glutathionylation and low TRPC1 expression (promoting TRPC5 homotetramer formation) were found in striatum of YAC128 HD transgenic mice and HD patients. S-glutathionylation assay (cysteine mutagenesis C176/C178), electrophysiology, Ca2+ imaging, TRPC5 knockdown/inhibition, YAC128 transgenic mice, human HD brain tissue Brain : a journal of neurology High 26133660
2019 Cryo-EM structure of mouse TRPC5 homotetramers resolved at 2.8 Å. The structure revealed a disulfide bond at the extracellular pore domain and differences in the extracellular pore domain and S3 helix length compared to other TRP channels. Mutagenesis confirmed the disulfide bond and a preceding loop are essential for TRPC5 function. Cryo-electron microscopy (2.8 Å resolution), electrophysiology, mutagenesis Science advances High 31355338
2023 Cryo-EM structures of human TRPC5-Gαi3 complexes at ~3 Å reveal a 4:4 stoichiometry in lipid nanodiscs. Gαi3 binds to the ankyrin repeat edge of TRPC5 ~50 Å from the membrane. Gαi3 increases TRPC5 sensitivity to PIP2, rendering the channel more easily opened under physiological PIP2 concentrations. Cryo-EM structure determination in lipid nanodiscs, electrophysiology (PIP2 sensitivity), structural modeling Nature communications High 37137991
2012 Gαi subunits are primary direct activators of TRPC5 (predominantly Gαi3) and TRPC4. Activation occurs through direct interaction of Gα with the conserved C-terminal SESTD domain of the channels. Two residues (K715 and R716) in TRPC4 mediate the Gαi2 interaction. Constitutively active Gαi mutants fully activate the channels. Co-immunoprecipitation, constitutively active Gα mutant expression, electrophysiology, structural modeling of SESTD-Gαi interaction, site-directed mutagenesis The Journal of biological chemistry High 22457348
2005 TRPC5 is activated by common endogenous lysophospholipids including lysophosphatidylcholine (LPC) independently of G-protein signaling. LPC activates TRPC5 in excised membrane patches, suggesting a relatively direct action on the channel structure. The effect shows dependence on acyl-chain length and head-group chemistry. Excised inside-out patch recordings, Ca2+-indicator dye measurements, G-protein pathway inhibition experiments in HEK293 cells The Journal of biological chemistry High 16368680
2008 Hypoosmotic stimulation and direct membrane stretch activate TRPC5 channels, causing Ca2+ influx. The osmotic response is blocked by GsMTx-4 (stretch-activated channel inhibitor) and requires PIP2; direct application of positive pressure through patch pipette also activates TRPC5. Activation is independent of PLC function. Whole-cell and excised patch-clamp, intracellular Ca2+ imaging, lipid phosphatase overexpression to deplete PIP2, pressure application via patch pipette in TRPC5-expressing cells The Journal of physiology High 18832422
2005 Calmodulin (CaM) binds to a novel C-terminal domain of TRPC5 (95 amino acids downstream from the CIRB domain), and exogenous CaM accelerates agonist-induced TRPC5 channel activation by ~2.8-fold. The CIRB domain is critical for overall receptor-induced TRPC5 activation. High intracellular Ca2+ (>5 µM) inhibits current density, demonstrating dual and opposite Ca2+ effects on TRPC5. Whole-cell patch-clamp, deletion mutagenesis, co-immunoprecipitation, surface expression assay in CHO and HEK293 cells The Journal of biological chemistry High 15987684
2006 Neuronal calcium sensor-1 (NCS-1) directly binds to the TRPC5 C-terminus and suppresses TRPC5 channel activity evoked by multiple stimuli. NCS-1 and TRPC5 are present in the same protein complex in rat brain. This NCS-1/TRPC5 complex contributes to retardation of neurite outgrowth. Co-immunoprecipitation from rat brain, in vitro pull-down binding assay, dominant-negative NCS-1 expression, patch-clamp electrophysiology The Journal of physiology High 16469785
2005 Ca2+-binding protein 1 (CaBP1) directly binds TRPC5 and inhibits its channel activity without affecting surface expression. CaBP1-binding sites on the TRPC5 C-terminus are closely localized to but distinct from CaM-binding sites. TRPC5 activity requires both extracellular and intracellular Ca2+. In vitro pull-down assay, two-electrode voltage clamp in Xenopus oocytes, surface expression assay, mutagenesis Pflugers Archiv : European journal of physiology High 15895247
2010 SESTD1, a phospholipid-binding protein containing SEC14-like and spectrin domains, associates with TRPC5 (and TRPC4) via the CIRB domain and is essential for efficient receptor-mediated activation of TRPC5. Phospholipid binding by SESTD1 is Ca2+-dependent. Yeast two-hybrid screen, Co-immunoprecipitation, in vitro phospholipid-binding assay, siRNA knockdown with electrophysiological readout The Journal of biological chemistry High 20164195
2005 TRPC5 activity is maintained by constitutive Ca2+-calmodulin/MLCK signaling that promotes plasma membrane localization of TRPC5. ML-9 (MLCK inhibitor) impaired membrane localization of TRPC5 and abolished channel activity in whole-cell recordings but not in excised inside-out patches. Whole-cell patch-clamp, inside-out patch-clamp, dominant-negative MLCK mutant expression, calmodulin inhibitor (W-13), surface localization assessment in HEK293 cells The Journal of physiology Medium 16284075
2004 The scaffolding protein EBP50 (NHERF1) modulates TRPC5 activation kinetics via the C-terminal VTTRL PDZ-binding motif. Co-expression of EBP50 caused significant delay in histamine-evoked TRPC5 activation; deletion of VTTRL abolished EBP50's modulatory effect without altering channel biophysical properties. Whole-cell patch-clamp, deletion mutagenesis (VTTRL motif), co-expression in HEK293 cells Journal of cellular physiology Medium 15334657
2007 Protons potentiate TRPC5 currents: lowering extracellular pH from 7.4 to 6.5 increases TRPC5 currents by reducing single-channel conductance while dramatically increasing open probability. The same glutamate residues responsible for lanthanide sensitivity (E543 and E595) mediate H+ potentiation. Whole-cell and single-channel patch-clamp, mutagenesis of E543Q and E595Q in HEK293 cells The Journal of biological chemistry High 17884814
2011 PKA directly inhibits TRPC5 channels via phosphorylation at Ser794 and Ser796. Constitutively active Gαs, isoproterenol, and 8-bromo-cAMP inhibit TRPC5 currents; this inhibition is abolished by S794A/S796A point mutations. PKA-mediated inhibition does not affect TRPC5 surface expression/trafficking. Whole-cell patch-clamp, site-directed mutagenesis (S794A, S796A), surface biotinylation, constitutively active Gαs expression in HEK293 cells American journal of physiology. Cell physiology High 21734191
2008 Complex regulation of TRPC5 by phosphatidylinositol 4,5-bisphosphate (PIP2): depletion of PIP2 via PI4-kinase inhibition activates TRPC5; inclusion of PIP2 in patch pipette inhibits TRPC5 currents; yet in excised patches PIP2 robustly activates TRPC5 single channels, demonstrating both inhibitory and stimulatory roles for PIP2 in regulating TRPC5. Whole-cell patch-clamp, excised single-channel recordings, PI4-kinase inhibition, targeted 5-phosphatase strategy, PIP2 infusion via patch pipette in HEK293 cells Pflugers Archiv : European journal of physiology High 18665391
2021 PIP2 controls both PKC-mediated desensitization and DAG/lanthanide-mediated activation of TRPC5 currents via gating regulation rather than by changing channel cell surface density. Optogenetically-controlled PIP2 dephosphorylation was used to dissect these mechanisms. Whole-cell patch-clamp, optogenetic PIP2 dephosphorylation tool, total internal reflection fluorescence microscopy for surface density in HEK293 cells The Journal of biological chemistry High 33933453
2013 The S4-S5 linker is a critical gating element in TRPC5. A conserved Gly504 to Ser substitution forces TRPC5 into a constitutively open conformation, causing Ca2+-dependent cell death. A second mutation (in the C-terminal S6 helix region) suppresses constitutive activation, suggesting an interaction between the S4-S5 linker and S6 in gating. Site-directed mutagenesis (G504S, double mutant), whole-cell patch-clamp, Ca2+-dependent cell death assay in HEK293 cells The Journal of biological chemistry High 23677990
2007 The first ankyrin-like repeat in the N-terminus is the minimum domain required for TRPC5 homomultimerization and functional assembly. Fragments lacking this repeat fail to multimerise, cannot interact with wild-type TRPC5, and do not form functional channels. N-terminal dominant-negative fragments retaining the first ankyrin repeat trap TRPC5 intracellularly. FRET measurements (CFP/YFP-labeled fragments), TIRF microscopy, electrophysiology, dominant-negative truncation analysis in HEK293 cells Cell calcium High 17624425
2014 Extracellular disulfide bonds between Cys553 and Cys558 in the pore loop are essential for TRPC5 tetramerization, trafficking to plasma membrane, and channel activity. C553S or C558S mutants lose all channel activity and act as dominant negatives. Reducing agents decrease membrane TRPC5 distribution. Cysteine mutagenesis (C553S, C558S), Co-immunoprecipitation, FRET analysis of dimerization, surface biotinylation, electrophysiology in HEK293 cells Pflugers Archiv : European journal of physiology High 24859801
2019 TRPC5 palmitoylation at a conserved cysteine residue is critical for intrinsic channel activity and membrane stability. Depalmitoylation reduces TRPC5 membrane stability and attenuates Ca2+-mediated striatal neurotoxicity in Huntington's disease cells. Palmitoylation assay, mutagenesis of palmitoylation site, membrane trafficking assay, electrophysiology in HD striatal cells (STHdh) Biochimica et biophysica acta. Molecular cell research Medium 31812495
2009 TRPC5 is activated by intracellular Ca2+ with an EC50 of ~635 nM at negative potentials; Ca2+ entry through either CRAC channels (STIM1/Orai1) or L-type voltage-gated Ca2+ channels is sufficient to activate TRPC5 via local subsarcolemmal Ca2+ increases (blocked by BAPTA but not EGTA). Whole-cell patch-clamp, caged Ca2+ photolysis, co-expression of STIM1/Orai1 and L-type Ca2+ channel subunits, EGTA vs BAPTA Ca2+ buffering comparison in HEK293 cells The Journal of biological chemistry High 19815560
2017 TRPC1, TRPC4, and TRPC5 assemble into heteromultimers with each other but not with other TRP family members in mouse brain and hippocampus. Loss of all TRPC1/4/5-containing channels reduces action potential-triggered EPSCs, impairs cross-frequency hippocampal network coupling, and causes deficits in spatial working memory but not reference memory. Quantitative high-resolution mass spectrometry (native complex identification), Trpc1/4/5 triple-KO mice, hippocampal slice electrophysiology (evoked EPSCs, LTP), in vivo hippocampal recordings, spatial memory tasks The EMBO journal High 28790178
2017 TrpC5 in POMC neurons mediates the acute anorexigenic effects of leptin and serotonin 2C receptor (Ht2Cr) agonists. POMC-specific TrpC5 deletion blocks leptin- and Ht2Cr agonist-induced membrane depolarization and reduces energy expenditure while increasing food intake and body weight. Conditional Pomc-specific Trpc5 KO mice, whole-cell patch-clamp electrophysiology in arcuate POMC neurons, metabolic phenotyping, feeding behavior assays Cell reports High 28099839
2019 Trpc5 deficiency impairs infraslow membrane potential oscillations of dopamine arcuate nucleus (ARC) neurons and prolactin-evoked tonic plateau potentials. Female Trpc5-mutant mice show severe hypoprolactinemia with associated reproductive deficits. Conditional Trpc5 KO mice, whole-cell patch-clamp in dopamine ARC neurons (brain slices), prolactin measurement, reproductive phenotyping Proceedings of the National Academy of Sciences of the United States of America High 31285329
2017 TRPC5 induces cytoprotective autophagy in breast cancer cells via the CaMKKβ/AMPKα/mTOR pathway, contributing to adriamycin resistance. Pharmacological inhibition or gene silencing of TRPC5 abolished this pathway and restored drug sensitivity in vitro and in vivo. siRNA knockdown, pharmacological inhibition, pathway inhibitors (CaMKKβ, AMPK, mTOR), autophagy markers (LC3), xenograft model Scientific reports Medium 28600513
2008 TRPC5 undergoes phase transitions in gating properties during the activation-deactivation cycle, shifting between outwardly-rectifying and doubly-rectifying I-V relationships. Mg2+ block mediated by cytoplasmic residue D633 underlies doubly-rectifying behavior at negative potentials. La3+ promotes channel transition to the doubly-rectifying (Phase 2) state. Whole-cell and single-channel patch-clamp, site-directed mutagenesis (D633), voltage-protocol analyses in HEK293 cells expressing rat TRPC5 Journal of cellular physiology Medium 18247362
2005 Junctate, an IP3R-associated protein, binds TRPC5 (and TRPC2) but not TRPC1 in sperm, as determined by pull-down experiments. The interaction is calcium-concentration-independent. Pull-down assay, co-immunoprecipitation, immunolocalization in rodent sperm Developmental biology Medium 16153633
2005 TRPC5 co-immunoprecipitates with Na+/K+-ATPase (NKA) pump from rat brain lysates, suggesting TRPC5 participates in a plasmalemmal signaling complex (signalplex) with cytoskeletal proteins (spectrin, actin, myosin, drebrin, tubulin, neurabin) and endocytic proteins (clathrin, dynamin, AP-2). Affinity-purified antibody immunoprecipitation from rat brain lysates, reciprocal Co-IP, mass spectrometry identification of interacting proteins Pflugers Archiv : European journal of physiology Medium 16025302
2010 In endothelial cells, TRPC6 activation by lysophosphatidylcholine (lysoPC) initiates Ca2+ influx that triggers translocation of TRPC5 to the plasma membrane, creating a TRPC6-TRPC5 channel cascade. The resulting prolonged Ca2+ elevation inhibits endothelial cell migration. TRPC5 externalization is dependent on upstream TRPC6 channel opening. siRNA knockdown of TRPC5 and TRPC6, TRPC6-/- mouse endothelial cells, surface biotinylation, Ca2+ imaging, cell migration assays Molecular biology of the cell High 18495872
2006 TRPC5-containing channels contribute to store-depletion-activated Ca2+ entry in smooth muscle cells of rabbit pial arterioles. An extracellular-loop-targeting anti-TRPC5 antibody (T5E3) suppressed Ca2+ entry in store-depleted arterioles but not in the absence of store depletion. T5E3 blocking antibody in freshly isolated arteriolar fragments, Ca2+ imaging, patch-clamp American journal of physiology. Heart and circulatory physiology Medium 16861696
2010 TRPC5 plasma membrane insertion via muscarinic stimulation contributes to cholinergic plateau potentials in hippocampal CA1 pyramidal neurons. Biotinylation assays showed that muscarinic stimulation specifically increased TRPC5 (not TRPC1 or TRPC4) surface expression in acute slices; PI3K inhibition (wortmannin) and CaM inhibition (W-7) blocked both TRPC5 insertion and the Ca2+ currents underlying plateau potentials. Surface biotinylation assay in acute hippocampal slices, whole-cell patch-clamp, pharmacological inhibition (2-APB, SKF96365, wortmannin, W-7), intracellular ATP perfusion Hippocampus High 20865744
2012 TRPC5 mediates NT-3 (neurotrophin-3)-induced Ca2+ influx in hippocampal neurons via PLCγ and TrkC signaling. Ca2+ influx through TRPC5 (not TRPC6) induced by NT-3 inhibits dendritic growth via CaMKIIα activation. siRNA knockdown of TRPC5, whole-cell patch-clamp, Ca2+ imaging, CaMKIIα inhibition, dendrite morphology analysis in rat hippocampal neurons The Journal of neuroscience : the official journal of the Society for Neuroscience High 22764246
2007 GM1 ganglioside cross-linking by cholera toxin B subunit (CtxB) activates TRPC5 channels to induce Ca2+ influx and neurite outgrowth in NG108-15 cells and primary cerebellar granule neurons. GM1 associates with α5β1-integrin (not directly with TRPC5), and the signaling cascade involves FAK autophosphorylation, PLCγ activation, and PI3K to open TRPC5. TRPC5 siRNA knockdown, Ca2+ imaging, PLCγ/PI3K/FAK pharmacological inhibition, confocal immunocytochemistry showing co-localization, TRPC5 KO neurons The Journal of neuroscience : the official journal of the Society for Neuroscience High 17626205
2009 In T effector cells, GM1 ganglioside cross-linking by galectin-1 (expressed by regulatory T cells) activates TRPC5 channels, causing Ca2+ influx that contributes to Treg-mediated suppression of Teff cell proliferation. TRPC5 shRNA knockdown blocked contact-dependent proliferation inhibition by Treg cells. shRNA knockdown of TRPC5, Ca2+ imaging, flow cytometry, T cell proliferation assays Journal of immunology Medium 19299701
2014 TRPC5-containing extracellular vesicles (EVs) from adriamycin-resistant breast cancer cells transfer TRPC5 protein to non-resistant recipient cells. Transferred TRPC5 activates NFATc3-mediated P-gp production through Ca2+ signaling, conferring chemoresistance on previously sensitive cells. EV isolation and transfer, TRPC5-siRNA treatment, Ca2+ signaling assays, P-gp expression by Western blot, xenograft mouse model Proceedings of the National Academy of Sciences of the United States of America Medium 24733904
2015 (-)-Englerin A is a potent, selective, and direct activator of TRPC4 and TRPC5 channels acting at a high-affinity extracellular binding site, rapidly killing renal cancer cells. Electrophysiology (patch-clamp), Ca2+ imaging, cell viability assays in TRPC4/5-expressing HEK cells and renal cancer cells Angewandte Chemie (International ed. in English) Medium 25707820
2018 Insulin and leptin depolarize hypothalamic POMC neurons via activation of TRPC5 channels, downstream of PI3K signaling. TRPC5 is identified as the specific downstream effector based on biophysical properties, pharmacological profile, and immunocytochemistry/single-cell RT-PCR localization. Whole-cell patch-clamp in mouse/rat/primate POMC neurons, pharmacological dissection, immunocytochemistry, single-cell RT-PCR, i.c.v. insulin injection with metabolic measurements Journal of neuroendocrinology High 28675783

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron 628 11301024
2000 Receptor-mediated regulation of the nonselective cation channels TRPC4 and TRPC5. The Journal of biological chemistry 348 10837492
2003 TRPC5 is a regulator of hippocampal neurite length and growth cone morphology. Nature neuroscience 302 12858178
2009 Essential role for TRPC5 in amygdala function and fear-related behavior. Cell 234 19450521
2010 Antagonistic regulation of actin dynamics and cell motility by TRPC5 and TRPC6 channels. Science signaling 224 20978238
2002 Lanthanides potentiate TRPC5 currents by an action at extracellular sites close to the pore mouth. The Journal of biological chemistry 220 12456670
2005 Block of TRPC5 channels by 2-aminoethoxydiphenyl borate: a differential, extracellular and voltage-dependent effect. British journal of pharmacology 217 15806115
2011 Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system. Proceedings of the National Academy of Sciences of the United States of America 194 22025699
2009 Cross-linking of GM1 ganglioside by galectin-1 mediates regulatory T cell activity involving TRPC5 channel activation: possible role in suppressing experimental autoimmune encephalomyelitis. Journal of immunology (Baltimore, Md. : 1950) 164 19299701
2015 (-)-Englerin A is a potent and selective activator of TRPC4 and TRPC5 calcium channels. Angewandte Chemie (International ed. in English) 163 25707820
2014 Essential role for TrpC5-containing extracellular vesicles in breast cancer with chemotherapeutic resistance. Proceedings of the National Academy of Sciences of the United States of America 162 24733904
2012 Transient receptor potential channel TRPC5 is essential for P-glycoprotein induction in drug-resistant cancer cells. Proceedings of the National Academy of Sciences of the United States of America 153 22988121
2007 Corticolimbic expression of TRPC4 and TRPC5 channels in the rodent brain. PloS one 143 17593972
2013 Inhibition of the TRPC5 ion channel protects the kidney filter. The Journal of clinical investigation 137 24231357
2003 TRPC4 and TRPC5: receptor-operated Ca2+-permeable nonselective cation channels. Cell calcium 133 12765689
2009 Intracellular calcium strongly potentiates agonist-activated TRPC5 channels. The Journal of general physiology 130 19398778
2003 TRPC5 as a candidate for the nonselective cation channel activated by muscarinic stimulation in murine stomach. American journal of physiology. Gastrointestinal and liver physiology 123 12631560
2008 Hypoosmotic- and pressure-induced membrane stretch activate TRPC5 channels. The Journal of physiology 116 18832422
2004 Human TRPC5 channel activated by a multiplicity of signals in a single cell. The Journal of physiology 113 15254149
2018 Treatment with HC-070, a potent inhibitor of TRPC4 and TRPC5, leads to anxiolytic and antidepressant effects in mice. PloS one 110 29385160
2012 Canonical transient receptor channel 5 (TRPC5) and TRPC1/4 contribute to seizure and excitotoxicity by distinct cellular mechanisms. Molecular pharmacology 110 23188715
2017 Heteromeric channels formed by TRPC1, TRPC4 and TRPC5 define hippocampal synaptic transmission and working memory. The EMBO journal 109 28790178
2011 Balancing calcium signals through TRPC5 and TRPC6 in podocytes. Journal of the American Society of Nephrology : JASN 106 21980113
2005 Sensing of lysophospholipids by TRPC5 calcium channel. The Journal of biological chemistry 104 16368680
2008 Complex functions of phosphatidylinositol 4,5-bisphosphate in regulation of TRPC5 cation channels. Pflugers Archiv : European journal of physiology 99 18665391
2015 Increased TRPC5 glutathionylation contributes to striatal neuron loss in Huntington's disease. Brain : a journal of neurology 91 26133660
2009 TRPC5 is a Ca2+-activated channel functionally coupled to Ca2+-selective ion channels. The Journal of biological chemistry 90 19815560
2006 Calcium-sensing mechanism in TRPC5 channels contributing to retardation of neurite outgrowth. The Journal of physiology 89 16469785
2007 Induction of calcium influx through TRPC5 channels by cross-linking of GM1 ganglioside associated with alpha5beta1 integrin initiates neurite outgrowth. The Journal of neuroscience : the official journal of the Society for Neuroscience 88 17626205
2017 TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons. Cell reports 87 28099839
2017 TRPC5-induced autophagy promotes drug resistance in breast carcinoma via CaMKKβ/AMPKα/mTOR pathway. Scientific reports 87 28600513
2012 Selective Gαi subunits as novel direct activators of transient receptor potential canonical (TRPC)4 and TRPC5 channels. The Journal of biological chemistry 85 22457348
2007 Potentiation of TRPC5 by protons. The Journal of biological chemistry 85 17884814
2019 Cryo-EM structure of TRPC5 at 2.8-Å resolution reveals unique and conserved structural elements essential for channel function. Science advances 84 31355338
2005 Calmodulin and calcium interplay in the modulation of TRPC5 channel activity. Identification of a novel C-terminal domain for calcium/calmodulin-mediated facilitation. The Journal of biological chemistry 81 15987684
2017 Increasing circulating exosomes-carrying TRPC5 predicts chemoresistance in metastatic breast cancer patients. Cancer science 79 28032400
2006 E3-targeted anti-TRPC5 antibody inhibits store-operated calcium entry in freshly isolated pial arterioles. American journal of physiology. Heart and circulatory physiology 78 16861696
2014 Clemizole hydrochloride is a novel and potent inhibitor of transient receptor potential channel TRPC5. Molecular pharmacology 72 25140002
2005 Proteomic analysis of TRPC5- and TRPC6-binding partners reveals interaction with the plasmalemmal Na(+)/K(+)-ATPase. Pflugers Archiv : European journal of physiology 72 16025302
2008 Elucidation of a TRPC6-TRPC5 channel cascade that restricts endothelial cell movement. Molecular biology of the cell 70 18495872
2005 Receptor-operated cation channels formed by TRPC4 and TRPC5. Naunyn-Schmiedeberg's archives of pharmacology 65 15902430
1999 Molecular cloning and characterization of TRPC5 (HTRP5), the human homologue of a mouse brain receptor-activated capacitative Ca2+ entry channel. Genomics 65 10493832
2004 TRPC5 activation kinetics are modulated by the scaffolding protein ezrin/radixin/moesin-binding phosphoprotein-50 (EBP50). Journal of cellular physiology 64 15334657
2010 Plasma membrane insertion of TRPC5 channels contributes to the cholinergic plateau potential in hippocampal CA1 pyramidal neurons. Hippocampus 59 20865744
2016 Transient receptor potential canonical 5 (TRPC5) protects against pain and vascular inflammation in arthritis and joint inflammation. Annals of the rheumatic diseases 58 27165180
2014 Tumor endothelial expression of P-glycoprotein upon microvesicular transfer of TrpC5 derived from adriamycin-resistant breast cancer cells. Biochemical and biophysical research communications 56 24582564
2011 A TRPC5-regulated calcium signaling pathway controls dendrite patterning in the mammalian brain. Genes & development 55 22135323
2011 Rapid and contrasting effects of rosiglitazone on transient receptor potential TRPM3 and TRPC5 channels. Molecular pharmacology 53 21406603
2005 Ca2+-calmodulin-dependent myosin light chain kinase is essential for activation of TRPC5 channels expressed in HEK293 cells. The Journal of physiology 53 16284075
2012 Calpain cleaves and activates the TRPC5 channel to participate in semaphorin 3A-induced neuronal growth cone collapse. Proceedings of the National Academy of Sciences of the United States of America 52 22547824
2014 TRPC5. Handbook of experimental pharmacology 51 24756705
2018 Insulin and leptin excite anorexigenic pro-opiomelanocortin neurones via activation of TRPC5 channels. Journal of neuroendocrinology 50 28675783
2010 Chemical physiology of oxidative stress-activated TRPM2 and TRPC5 channels. Progress in biophysics and molecular biology 50 20553742
2005 Inhibition of TRPC5 channels by Ca2+-binding protein 1 in Xenopus oocytes. Pflugers Archiv : European journal of physiology 50 15895247
2021 PIP2 regulation of TRPC5 channel activation and desensitization. The Journal of biological chemistry 49 33933453
2014 Riluzole activates TRPC5 channels independently of PLC activity. British journal of pharmacology 47 24117252
2019 Discovery of a Potent and Selective TRPC5 Inhibitor, Efficacious in a Focal Segmental Glomerulosclerosis Model. ACS medicinal chemistry letters 45 31749913
2011 Stereo-selective inhibition of transient receptor potential TRPC5 cation channels by neuroactive steroids. British journal of pharmacology 45 21108630
2005 Distribution of TRPC1 and TRPC5 in medial temporal lobe structures of mice. Cell and tissue research 45 16044320
2005 Junctate, an inositol 1,4,5-triphosphate receptor associated protein, is present in rodent sperm and binds TRPC2 and TRPC5 but not TRPC1 channels. Developmental biology 45 16153633
2017 Overexpression of TrpC5 promotes tumor metastasis via the HIF-1α-Twist signaling pathway in colon cancer. Clinical science (London, England : 1979) 44 28864720
2015 Plasma membrane mechanical stress activates TRPC5 channels. PloS one 44 25849346
2012 Neuroepithelial bodies as mechanotransducers in the intrapulmonary airway epithelium: involvement of TRPC5. American journal of respiratory cell and molecular biology 44 22461428
2016 Elevated expression of TrpC5 and GLUT1 is associated with chemoresistance in colorectal cancer. Oncology reports 43 28000878
2011 Properties and therapeutic potential of transient receptor potential channels with putative roles in adversity: focus on TRPC5, TRPM2 and TRPA1. Current drug targets 43 21291387
2010 The phospholipid-binding protein SESTD1 is a novel regulator of the transient receptor potential channels TRPC4 and TRPC5. The Journal of biological chemistry 43 20164195
2015 Identification and optimization of 2-aminobenzimidazole derivatives as novel inhibitors of TRPC4 and TRPC5 channels. British journal of pharmacology 42 25816897
2019 Review of Transient Receptor Potential Canonical (TRPC5) Channel Modulators and Diseases. Journal of medicinal chemistry 40 30943030
2016 Natural and synthetic flavonoid modulation of TRPC5 channels. British journal of pharmacology 40 26565375
2013 Conserved gating elements in TRPC4 and TRPC5 channels. The Journal of biological chemistry 39 23677990
2012 Effect of non-steroidal anti-inflammatory drugs and new fenamate analogues on TRPC4 and TRPC5 channels. Biochemical pharmacology 38 22285229
2015 Functional interplay between ganglioside GM1 and cross-linking galectin-1 induces axon-like neuritogenesis via integrin-based signaling and TRPC5-dependent Ca²⁺ influx. Journal of neurochemistry 37 26526326
2011 Opposite regulatory effects of TRPC1 and TRPC5 on neurite outgrowth in PC12 cells. Cellular signalling 37 22201561
2017 TRPC5 Does Not Cause or Aggravate Glomerular Disease. Journal of the American Society of Nephrology : JASN 36 29061651
2012 TRPC5 channel is the mediator of neurotrophin-3 in regulating dendritic growth via CaMKIIα in rat hippocampal neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 35 22764246
2012 The roles of G proteins in the activation of TRPC4 and TRPC5 transient receptor potential channels. Channels (Austin, Tex.) 35 22878724
2018 The TRPC5 channel regulates angiogenesis and promotes recovery from ischemic injury in mice. The Journal of biological chemistry 34 30413532
2019 TRPC1 as a negative regulator for TRPC4 and TRPC5 channels. Pflugers Archiv : European journal of physiology 33 31222490
2023 Molecular architecture of the Gαi-bound TRPC5 ion channel. Nature communications 32 37137991
2021 Safety and Efficacy of GFB-887, a TRPC5 Channel Inhibitor, in Patients With Focal Segmental Glomerulosclerosis, Treatment-Resistant Minimal Change Disease, or Diabetic Nephropathy: TRACTION-2 Trial Design. Kidney international reports 32 34622097
2019 Trpc5 deficiency causes hypoprolactinemia and altered function of oscillatory dopamine neurons in the arcuate nucleus. Proceedings of the National Academy of Sciences of the United States of America 32 31285329
2016 TrpC5 regulates differentiation through the Ca2+/Wnt5a signalling pathway in colorectal cancer. Clinical science (London, England : 1979) 32 27895148
2010 Genistein potentiates activity of the cation channel TRPC5 independently of tyrosine kinases. British journal of pharmacology 31 20233211
2010 TRPC5 channel sensitivities to antioxidants and hydroxylated stilbenes. The Journal of biological chemistry 31 21127073
2006 Cellular localization of TRPC5 in the substantia nigra of rat. Neuroscience letters 31 16635549
2015 The contribution of TRPC1, TRPC3, TRPC5 and TRPC6 to touch and hearing. Neuroscience letters 29 26520460
2008 TRPC5 channels undergo changes in gating properties during the activation-deactivation cycle. Journal of cellular physiology 29 18247362
2014 Intragenic rearrangements in X-linked intellectual deficiency: results of a-CGH in a series of 54 patients and identification of TRPC5 and KLHL15 as potential XLID genes. American journal of medical genetics. Part A 28 24817631
2018 TRPC4/TRPC5 channels mediate adverse reaction to the cancer cell cytotoxic agent (-)-Englerin A. Oncotarget 27 30038709
2017 A benzothiadiazine derivative and methylprednisolone are novel and selective activators of transient receptor potential canonical 5 (TRPC5) channels. Cell calcium 27 28807145
2014 Extracellular disulfide bridges stabilize TRPC5 dimerization, trafficking, and activity. Pflugers Archiv : European journal of physiology 27 24859801
2007 The first ankyrin-like repeat is the minimum indispensable key structure for functional assembly of homo- and heteromeric TRPC4/TRPC5 channels. Cell calcium 27 17624425
2019 TRPC5‑induced autophagy promotes the TMZ‑resistance of glioma cells via the CAMMKβ/AMPKα/mTOR pathway. Oncology reports 26 30942446
2018 Contribution of Zinc-Dependent Delayed Calcium Influx via TRPC5 in Oxidative Neuronal Death and its Prevention by Novel TRPC Antagonist. Molecular neurobiology 26 30062674
2011 Molecular determinants of PKA-dependent inhibition of TRPC5 channel. American journal of physiology. Cell physiology 26 21734191
2008 Modulation of TRPC5 cation channels by halothane, chloroform and propofol. British journal of pharmacology 26 18204473
2019 TRPC5 channel instability induced by depalmitoylation protects striatal neurons against oxidative stress in Huntington's disease. Biochimica et biophysica acta. Molecular cell research 24 31812495
2018 TRPC5-eNOS Axis Negatively Regulates ATP-Induced Cardiomyocyte Hypertrophy. Frontiers in pharmacology 24 29872396
2010 Nitric oxide lacks direct effect on TRPC5 channels but suppresses endogenous TRPC5-containing channels in endothelial cells. Pflugers Archiv : European journal of physiology 24 20390293
2020 Isoliquiritigenin Inhibits Atherosclerosis by Blocking TRPC5 Channel Expression. Cardiovascular therapeutics 23 32328171

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