TRPC5 | Transient Receptor Potential Cation Channel Subfamily C Member 5

Family:
Transient  receptor potential channels

Subgroups:
TRPC (TRPC1–TRPC7), TRPV (TRPV1-TRPV6), TRPA1, TRPM (TRPM1–TRPM8), TRPP (TRPP1–TRPP3, PKD1, PKDREJ, PKDL1–PKDL3), TRPML (TRPML1–TRPML3), TRPN

Topology:
Most TRP channels are composed of 6 transmembrane domains (helices) with intracellular N- and C-termini, non-selectively permeable to various cations

TRPC5: Background information

TRPC5, aslo called Short transient receptor potential channel 5 or transient receptor protein 5 is a multi-pass membrane protein and is thought to form a receptor-activated non-selective calcium permeant cation channel. The protein is active alone or as a heteromultimeric assembly with TRPC1, TRPC3, and TRPC4. TRPC5 has been implicated in the mechanism of mercury toxicity and neurological behavior

Gene:
SCN10A

Human Protein:
UniProt Q9UL62

Tissue:
Brain, adult heart, testis, ovaries

Function/ Application:
Pressure sensing, TRPC5 counteracts TRPC1 in regulating neurite outgrowth and appears to be involved in growth cone collapse that occurs when the growth cone detects a repellant factor

Pathology:
Hypertrophic Pyloric Stenosis

Interaction:
TRPC1, TRPC3, TRPC4, calmodulin, CABP1, enkurin, Na+–H exchange regulatory factor, interferon-induced GTP-binding protein, ring finger protein 24, SEC14 domain and spectrin repeat-containing protein 1, Calcium channel, voltage-dependent, gamma subunit, Mitochondrial calcium uniporter 3

Modulator:
Thioredoxin

Assays:
Patch Clamp: whole cell

Particularities:

Ligand-gated ion channel, as well as mechano-sensitive ion channel

Recommended Reviews:
International Union of Pharmacology. XLVII. Nomenclature and Structure-Function Relationships of Voltage-Gated Sodium Channels. Pharmacol Rev 57: 397–409, Catterall, et al. 2005 

Data and Applications

TRPC5 - Block by Gadolinium

TRPC5icon pl   Patchliner data and applications: 
Data are taken from Milligan C.J. et al., Nature Protocols, 2009, 4(2), 244-255.

Current voltage relationships showing activaion of TRPC5 by extracellular application of Gd3+ (100 μM). Voltage ramps (−100 mV to 100 mV, holding potential 0 mV) were for 1s at 0.1 Hz.

Application Notes

TRPC5 - "Internal perfusion of Ca2+ to activate hTRPC5 on Nanion's SyncroPatch 384PE"

icon sp96   SyncroPatch 384PE application note   logo pdf   (1.7 MB)
Cells were kindly provided by Charles River.

Posters

Publications

2018 - Design, synthesis and characterization of novel N-heterocyclic-1-benzyl-1H-benzo[d]imidazole-2-amines as selective TRPC5 inhibitors leading to the identification of the selective compound, AC1903

icon sp96   SyncroPatch 384PE article in Bioorganic and Medicinal Chemistry Letters (2018)

Authors:
Sharma, S.H., Pablo J.L., Montesinos, M.S., Greka, A., Hopkins, C.R.

2011 - Rapid and Contrasting Effects of Rosiglitazone on Transient Receptor Potential TRPM3 and TRPC5 Channels

icon pl  Patchliner publication in Molecular Pharmacology (2011)

Authors: 
Majeed Y., Bahnasi Y., Seymour V.A.L., Wilson L.A., Milligan C.J., Agarwal A.K., Sukumar P., Naylor J., Beech D.J.

2009 - Robotic multiwell planar patch-clamp for native and primary mammalian cells

icon pl  Patchliner publication in Nature Protocols (2009)

Authors:
Milligan C.J., Li J., Sukumar P., Majeed Y., Dallas M.L., English A., Emery P., Porter K.E., Smith A.M., McFadzean I., Beccano-Kelly D., Bahnasi Y., Cheong A., Naylor J., Zeng F., Liu X., Gamper N., Jiang L., Pearson H.A., Peers C., Robertson B., Beech D.J.

2008 - TRPC channel activation by extracellular thioredoxin

icon pl  Patchliner publication in Nature (2008)

Authors: 
Xu S.Z., Sukumar P., Zeng F., Li J., Jairaman A., English A., Naylor J., Ciurtin C., Majeed Y., Milligan C.J., Bahnasi Y.M., Al-Shawaf E., Porter K.E., Jiang L.H., Emery P., Sivaprasadarao A., Beech D.J.

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