Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Transient Receptor Potential Cation Channel Subfamily C Member 5

Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101908


Historical Background

TRPC5 is a member of the canonical family of transient receptor potential (TRP) channels, forming a subgroup along with TRPC1 and TRPC4. TRPC5 has been cloned from the mouse (Okada et al. 1998; Philipp et al. 1998), rabbit (Philipp et al. 1998), and humans, lying in the Xq23 region of the latter, a region that contains loci for nonsyndromic mental retardation and two genes implicated in X-linked disorders. The TRPC5 protein forms homomers and heteromers with TRPC1, TRPC3, TRPC4, and TRPC6 (Strubing et al. 2001). Like other members of the TRPC family, TRPC5 is a nonselective cationic channel that permits the flow of calcium, sodium, cesium, and potassium ions, although with greater selectivity for Ca2+. Cation selectivity varies in the literature, from PCa2+/PNa+ = 14.3 (Okada et al. 1998) to PCa2+/PNa+ = 1.79 (Schaefer et al. 2000). When overexpressed, TRPC5 forms functional plasma membrane channels activated by a broad range of physiological voltages, and although it is not considered a “voltage gated” channel, voltage can modulate the channel once it is activated by other mechanisms. Many different molecules and compounds can activate TRPC5, as well as stretch and temperature. Like TRPC4, activation of the homomeric TRPC5 channel assembly provokes asymmetric inward and outward rectification, with a single channel conductance of ∼40 pS at −60 mV. The blockage of the channel between 0 and +60 mV is dependent on Mg2+, while above +80 mV the conductance is more than two-fold that at negative potentials (Schaefer et al. 2000; Strubing et al. 2001). Direct or indirect activation of TRPC5, for example, by activating G protein coupled receptors (GPCRs), provokes transient increases in current, described as a double rectifying current with a flat region around the reversal potential, a clear hallmark of this channel (Fig. 1).
Transient Receptor Potential Cation Channel Subfamily C Member 5, Fig. 1

Current-voltage relationship evoked by a 400-ms duration voltage ramp from −100 to +100 mv applied during carbachol (10 μM) application to HEK293 cells co-expressing TRPC5 and the muscarinic type 1 acetylcholine receptor. Note the characteristic doubly rectifying shape of the TRPC5-mediated current and the reversal potential close to 0 mV

TRPC5 interacts with a long list of different proteins including other members of the TRPC channel family. The formation of heteromultimers with other TRPC channels has been well studied for TRPC1, and TRPC5-TRPC1 complexes form functional nonselective calcium channels in the brain but with a different I/V relationship and a distinct calcium permeability (Strubing et al. 2001) to homomeric TRPC5. A complete list of interacting proteins identified to date is available at http://trpchannel.org/summaries/TRPC5, and some of the well-characterized TRPC5 protein interactions have been reviewed elsewhere (Zholos 2014).


Human TRPC5 contains 973 amino acids, as opposed to 975 in mice and 974 for most other species, and its sequence is highly conserved across species (i.e., 99% human vs. Rhesus monkey or 96.9% human vs. mice). TRPC5 is a membrane protein with a core of six transmembrane segments linked by extracellular and intracellular segments of differing size and with flanking N and C-terminal regions on the cytoplasmic site (Okada et al. 1998). When four subunits assemble to build a channel, a region between the S5 and S6 segments forms a pore. TRPC5 shares 68.5% sequence identity with TRPC4, both containing a PDZ-domain binding VTTRL motif in the C-terminal tail (Ct) that interacts with the Na+/H+ exchanger regulatory factor (NHERF, also known as EBP50), a scaffolding protein that modulates channel activation kinetics (Obukhov and Nowycky 2004). The C-terminus also contains a TRP box (EWKFAR, the most conserved region of TRP channels), a highly conserved proline-rich motif downstream of the TRPC box, two calmodulin-binding sites, and a predicted coiled-coil region (CCR) (Fig. 2). The N-terminus (Nt) contains one calmodulin-binding site, a CC region, a putative caveolin-binding region, and two well-conserved ankyrin repeats (Fig. 2).
Transient Receptor Potential Cation Channel Subfamily C Member 5, Fig. 2

Simplified scheme illustrating the molecular structure of TRPC5, the intracellular pathways and intracellular messengers with which it may interact, and the agonists and physical stimuli that may regulate the activity of the TRPC5 channel. 1. Channel structure. TRPC5 consists of six transmembrane segments (S1–S6) with a pore-forming region between TS5–TS6. The N-terminal intracellular region contains a calmodulin-binding domain (CaMB), a coiled-coil region (CCR), and two ankyrin repeats. The C-terminal domain contains the conserved TRP box, the calmodulin and IP3 binding domain (CIRB), the CCR, a second CaMB, and the VTTRL PDZ-domain binding site. 2. Signaling activation. Activation of GPCRs initiates the PLC and PKA signaling cascades. PLC activation generates IP3 and DAG from PIP2. IP3 release Ca2+ from internal stores, while DAG does not affect the channel. Low concentrations of intracellular Ca2+ activate TRPC5, whereas high micromolar concentrations of Ca2+ inhibit this channel. In addition, calcium release from the stores promotes the translocation of TRPC5 to the plasma membrane. Activation of PKA inhibits TRPC5. 3. TRPC5 Activators. A variety of compounds activate the channel through a common mechanism that involves an interaction with glutamic acid (Glu; green) and cysteine residues (Cys; pink). 4. Physical stimulation. Membrane stretch and cooling directly activate or modulate the channel

Structure-function studies of the channel suggest different roles for these conserved regions in members of the TRPC family, although the specific roles of these motifs in TRPC5 are not fully clear. It has been suggested that the ankyrin repeats form an interaction domain for different binding partners, while the proline-rich motive mediates interactions with other proteins and the caveolar region could be involved in channel targeting to the plasma membrane (as for TRPC1). One of the two Ct calmodulin-binding sites (named the CIRB) binds to the IP3 receptor, and both are involved in the modulation of TRPC5 when it is activated by agonists. The CC region in the Nt interacts with the Nt of adjacent TRPC channels and the CC region in the Ct interacts with both the Nt and Ct of contiguous units, contributing to the homo- and heteromerization of the channel. It has been shown that the CC region in the Ct of TRPC5 interacts with the stathmin family of proteins, the TRPC5 complex specifically interacting with the stathmin 2 in cytoplasmic transport vesicles (Greka et al. 2003). A more extensive review of the structure of TRPC5 can be found elsewhere (Zholos 2014).


TRPC5 has been detected in different tissues, and it exhibits the most specific expression of any TRPC channel in the central nervous system. It is strongly expressed in the human fetal and adult brain, and in the latter TRPC5 is expressed particularly strongly in the cerebellum, amygdala, cingulate gyrus, and cerebral cortex. By contrast, TRPC5 is more weakly expressed in the locus coereleus, nucleus accumbens, thalamus, medulla oblongata, and parahippocampus, and two-fold lower in the putamen, striatum, substantia nigra, and spinal cord.

In rodents, TRPC5 and TRPC4 are the TRPC channels most strongly expressed in the brain. TRPC5 is expressed in neurons of the lateral cerebellar nucleus, in the prefrontal, orbitofrontal, entorhinal, auditory, and somatosensory cortex, in hippocampal pyramidal neurons, in the amygdala and hypothalamus, and in the mitral cell layer and the glomerular layer of the olfactory bulb. TRPC5 and TRPC4 are co-expressed in some tissues, like the hippocampus; however, TRPC4 is expressed in the internal granular layer in the olfactory bulb and not in the glomerular layer. TRPC5, TRPC4, and TRPC1 are all co-expressed in the hippocampus and basal ganglia, suggesting that heteromultimers may form there. TRPC5 is also expressed by visceral sensory neurons and by the trigeminal and dorsal root ganglia neurons.

Beyond the nervous system, TRPC5 is moderately or weakly expressed in the heart, liver, muscle, pancreas, kidney, cartilage, gonads, lung, and adrenal gland, as well as in the endothelium of the coronary arteries and in the vascular and gastric smooth muscle.

Activators and Inhibitors (Modulators)

TRPC5 is activated by a wide variety of molecules, compounds, and physical stimuli (for a summary of the TRPC5 modulators and a complete list see Fig. 2 and Table 1), although it was initially identified as a receptor operated channel (Philipp et al. 1998; Schaefer et al. 2000). It is activated by receptors that couple to phospholipase C (PLC), although the molecular mechanisms underlying this activation are not completely understood. It has been shown that TRPC5 channels can be activated by GPCRs (Gαq/11) through PLC-β (e.g., M3 muscarinic acetylcholine, bradykinin, and H1 histamine receptors) or by tyrosine kinases coupled to PLC-γ2 (EGF receptor). This activation is thought to be independent of store depletion, DAG and InsP3Rs, although dependence on InsP3Rs remains uncertain. In gastric smooth muscle, significant activation of TRPC5 is also caused by stimulation of Gαi-coupled receptors (M2 muscarinic acetylcholine receptor), specifically by Gαi3 through the direct activation of the channel by Gαi subunits. In a heterologous system, activation of the Gαs cascade by stimulating β-adrenergic receptors evokes IP3-mediated Ca+2 release, which in turn activates TRPC5 (Fig. 2).
Transient Receptor Potential Cation Channel Subfamily C Member 5, Table 1

Activators of the TRPC5 channels. For a more extensive information and references, see Beech (2013)

Signaling molecules

Mode of action


Agonists of GPCRs that couple to Gαq/11

PLC dependent

DAG independent


Agonists of GPCRs that couple to Gαi/o

Direct interaction Gαi subunit- SESTD1B


Agonists GPCRs that couple to Gαs

Ca2+ release mediated by IP3R


Receptor Tyrosine Kinases

PLC dependent


Intracellular Ca2+ (submicromolar)

Calmodulin-CIRB/CBII interaction

Different signaling pathways

Membrane potential;

(−) EC50 = 635.1 nM

(+) EC50 = 358.2 nM


Activation of GPCRs


Chemical factors

La3+ and Gd3+ (micromolar)


Glu543 and Glu595


Protons (H+)


Glu543 and Glu595

pH = 6.87



≈ 5 μM


Cys553 and Cys558

MeHg =2.03 μM

HgCl2 = 3.07 μM





Cys553, Cys558



Cys553, Cys558


Genistein and Daidzein

Independent of GPCRs, PLC and tyrosine Kinases

93 μM



≈ 30 μM

(−)-Englerin A

Independent of GPCRs

7.6 nM


Independent of GPCRs and PLC, independent of E595/E598

9.2 ± 0.5 μM

Lipidic factors




Independent of PLC



Acting through Go/iPCRs


Oxidized phospholipids

Acting through Go/iPCRs

PGPC = 2.24 μM

POVPC = 1.52 μM





GM1 ganglioside

PLC dependent


Physical factors




Temperature range 37–25 °C

Membrane stretch/hypotonicity

Independent of PLC


The effect of inositol lipids is also unclear, due to the distinct results obtained with different strategies to modify their levels. Pharmacological inhibition of PIP and PIP2 activates TRPC5, while depletion of PIP2 with a targeted 5-phosphatase inhibits the activity of the channel (Trebak et al. 2009). This channel is also activated by intracellular Ca2+ although the role of calcium in TRPC5 activation remains controversial and high micromolar concentrations of Ca2+ are inhibitory to this channel (reviewed in Zholos 2014). Calmodulin (CaM) is a common intracellular mediator of many Ca2+-dependent events, and the CaM-IP3 binding site (CIRB) in TRPC5 competes with one of the more downstream C-terminal CaM binding sites (CBII) to modulate the receptor-agonist activation of the channel. CBII is important for the Ca2+/CaM-mediated facilitation of channel activation, whereas the CIRB domain is critical for the overall response of the channel to receptor-agonist activation, particularly as disrupting the CIRB domain of TRPC5 blocks receptor-agonist activation. The intracellular Ca2+ affinity for CaM binding to CBII is more than 10 times higher than that to the CIRB site, such that high (>5 μm) intracellular-free Ca2+ inhibits the current density without affecting the rate of channel activation (Ordaz et al. 2005).

It has been proposed that TRPC5 acts as a direct sensor of lysophospholipids, suggesting that this channel is sensitive to the structure of the lipid bilayer. An exclusive characteristic of TRPC4 and TRPC5 is that their activation is modulated by the lanthanides, La3+ and Gd+3. This modulation is concentration dependent, and at micromolar concentrations, the channel’s open probability increases, whereas it is inhibited at millimolar concentrations. These effects involve interactions with the glutamic acid residues situated close to the extracellular mouth of the channel pore, Glu543 and Glu595/598, yet their biological relevance has not been elucidated (Fig. 2).

TRPC5 is proposed to be involved in sensing gaseous signaling molecules and in regulating the redox status of the cell. It has been show that TRPA1, TRPV1, and TRPC5 are directly activated by reactive oxygen species (ROS) and reactive nitrogen species (RNS) through a common mechanism, the modification of Cys residues or S-nitrosylation. TRPC5 channels are activated directly by H2O2 and nitric oxide (NO) through the modification of Cys residues. NO is a short-lived reactive molecule that serves as an important gaseous signal involved in endothelial-dependent vascular relaxation, cell motility, immune defense, and neurite outgrowth. Application of the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) or H2O2 to TRPC5-expressing HEK293 cells, or to bovine aortic endothelial cells that natively express TRPC5, causes robust influx of Ca2+. Mutation of Cys553 and Cys558 to serine in the putative pore-forming region between the fifth and sixth transmembrane regions of mouse TRPC5 dampens the response to NO (Yoshida et al. 2006). The Cys533 residue is also important for other aspects of TRPC5 activity, and this highly conserved cysteine residue in the extracellular pore loop of TRPC5 forms a disulfide bridge between TRPC5 monomers, thereby participating in multimer formation. However, questions have been raised regarding the activation of TRPC5 by SNAP, possibly reflecting differences in the NO sensitivity of TRPC5 in distinct culture conditions, how the drugs are administered, cell density, antioxidant levels and other experimental conditions, or the influence of the molecular and cellular status of the cell.

Thioredoxin (TRX) is another important intracellular and secreted redox protein with established biological roles in cancer, ischemia reperfusion injury, inflammation, and aging. TRX is reduced by the NADPH-dependent flavoprotein thioredoxin reductase and it can break disulfide bridges in this state. Secreted reduced thioredoxin (rTRX) acts as an agonist of TRPC5 homomers and TRPC5–TRPC1 heteromultimeric channels by breaking a disulfide bridge in the predicted extracellular loop, adjacent to the ion-selectivity filter of TRPC5 (Xu et al. 2008).

Regarding the activation of TRPC5 by physical factors, hypoosmotic- and pressure-induced membrane stretching can activate TRPC5 (Gomis et al. 2008). This activation is independent of PLC signaling, although it requires permissive levels of PIP2 in the plasma membrane. Membrane stretch activation of TRPC5 was blocked by the toxin GsMTx-4, an inhibitor of stretch and mechanical activated channels.

Monomeric TRPC5 channels have a high gating sensitivity to cooling in the range of 37–25 °C, activation that is potentiated by GqPCRs. Deletion of TRPC5 in mice did not modify the behavioral responses to temperature, although the loss of TRPC5 resulted in changes in the response properties of cold-sensitive C-mechano afferent fibers (Zimmermann et al. 2011).

Less is known about the direct or indirect inhibitors of TRPC5 (see Table 2). Some signaling molecules have dual effects on TRPC5 depending on their concentration, such as intracellular calcium and lanthanides (see above). PKC phosphorylation of T972 desensitizes the channel and phosphorylation by PKA at serine residues 794 and 796 inhibits the channel. Stimulation of β-adrenergic receptors activates the Gαs cascade, which further activates PKA that in turn phosphorylates and inhibits TRPC5. Moreover, 2-APB blocks TRPC5-mediated currents by interacting with amino acids in and around the ion pore of the channel.
Transient Receptor Potential Cation Channel Subfamily C Member 5, Table 2

Inhibitors of the TRPC5 channels. For a more extensive information and references see Beech (2013)

Signaling molecules

Mode of action


PKC activation


Phosphorylation of T972


PKA activation

Phosphorylation S794 and S796


Intracellular Ca2+ (micromolar)



Lock of GPCRs in inactive state


Chemical factors

La3+ and Gd3+ (millimolar)

Glu543 and Glu595




457 μM

ATP intracellular






0.45 μM

2-Aminobenzimidazole derivates (M084)


8.2 μM

Clemizole hydrochloride

Direct block

1.0–1.3 μM


Direct in extracellular sites

19 μM


Independent of PLC


Flufenamic acid (FFA), mefenamic acid (MFA), niflumic acid (NFA), and diclofenac sodium (DFS)


FFA = 37 ± 5 μM

MFA = 80 ± 5 μM

NFA = 80 ± 9 μM

DFS = 170 ± 9 μM

BTP2 (Pyr2)


0.1–1 μM



1.38 μM

Anesthetics (Chloroform, halothane, and propofol)


Chloroform =0.11 mM

Halothane =0.22 mM

Propofol =84.5 μM

Antioxidants (Vitamin C, Gallic acid)

Only H2O2 and GD3+ responses


Antioxidants (Trans-resveratrol)


10 μM


Direct blockade

4–9 μM

Sigma-1 receptor ligands (4-IBP, BD1047 and BD1063)

Direct blockade, independent of sigma-1 receptor


Lipidic factors



Neuroactive steroids


Pregnenolone sulfate = 19 μM; Progesterone =5 μM



13.6 μM

ω-3 fatty acids (α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid)


α-linolenic acid =21.5 μM

The gaseous anesthetics halothane and chloroform also appear to inhibit the activation of TRPC5 evoked by the agonist of muscarinic receptors carbachol, Gd+3 or LPC. However, the modulatory effect of the intravenous propofol is more complex, showing inhibitory and stimulatory effects. Other negative modulators of TRPC5 are listed in Table 2.

Regulation of TRPC5

Beside the direct and indirect activation of TRPC5 at the plasma membrane, the channel can be transported from the cell body to the growth cones or to more distal membrane domains. Like other TRP channels, TRPC5 channels are constitutively active, but it is possible that a pool of TRPC5 remains in the cytoplasm or in vesicles ready to be inserted into the plasma membrane in order to regulate the morphology of the cells or to potentiate its responses to a specific stimulus. TRPC5 forms a complex with Stathmin 2, a phosphoprotein involved in microtubule dynamics and cytoplasmic vesicle transport, and in this way it is carried to the growth cones of hippocampal neurons (Greka et al. 2003).

TRPC5 is rapidly translocated and inserted into the plasma membrane after stimulation of growth factor receptors via Rac, phosphatidylinositol 3 kinase (PI3K), and phosphatidylinositol 4-phosphate 5-kinase (PIP5K; Bezzerides et al. 2004), as well as by muscarinic stimulation and activation of Gαs.

Osmotic stress activation of TRPC5 is further potentiated by osmotic modulation of the G protein-coupled H1R and of PLC-coupled and Ca2+-dependent signaling pathways, regulating the membrane insertion of this channel (Jemal et al. 2014). Gq-coupled receptors are endogenously expressed in all cell types, and thus, membrane stress may produce enhanced responses in cells co-expressing TRPC5 and GPCRs. This synergistic mechanism may be particularly relevant in the vascular system, contributing to cell motility or the sensing of arterial pressure.

Physiological Role

Until recently, the biological role of TRPC5 was unknown. At the cellular level, the first physiological role attributed to TRPC5 was the regulation of neurite extension and growth-cone morphology (Greka et al. 2003). In developing hippocampal neurons, TRPC5 co-localizes with the synaptic vesicle proteins VAMP and synaptotagmin in punctate structures. A model has been proposed in which the channel is synthesized in the cell body and it is then transported in vesicles to the growth cone and newly forming synapses. Insertion of TRPC5 into growth cones restricts filopodium and neurite length. TRPC5 channels also mediate receptor-operated Ca2+ entry, regulating the Ca2+ waves produced during neuronal differentiation, and thus, Ca+2 waves are thought to be the link between external stimuli and growth cone morphology and motility. TRPC5 also participates in different regulatory aspects of neuronal growth through its interaction with Ca2+/CaM kinase IIα or NCS-1, and it also participates in the regulation of motor neuron axon pathfinding via Plexin A3 receptors. In nonneuronal cells TRPC5 may also play a regulatory role in cell migration and motility (reviewed in Zholos 2014).

The generation of TRPC5 KO mice has allowed us to learn more about the possible physiological roles of this channel. TRPC5−/− mice do not display defects in weight, spontaneous behavior, neurological reflexes, sensorimotor responses, or overall spontaneous locomotor activity. Since TRPC5 is most strongly expressed in the areas of the brain responsible for learning and fear, KO mice were evaluated in different tests related to such behaviors. As a result, TRPC5−/− mice apparently display less innate fear than wild-type mice. Moreover, TRPC5 may participate in the conditioning of fear memory under certain training conditions (Riccio et al. 2009). These behaviors appear to result from the loss of CCK2 or metabotropic glutamate-receptor activation/potentiation of excitatory permeant TRPC5 channels.

TRPC5 is expressed in endothelial and vascular smooth muscle cells, although its function is not fully clear as it is not always detected in these tissues and its expression may depend on important vascular modulators or conditions. However, there is evidence that TRPC5 is involved in vascular diseases, such as atherosclerosis. Sphingosine-1-phosphatase (S1P), a phospholipid that accumulates in atherosclerotic lesions and in ischemia, evokes vascular smooth muscle cell motility through a mechanism that involves homomultimers of TRPC5 or heteromultimers of TRPC5 and TRPC1. TRPC5 is a target for S1P, which is activated through intracellular and extracellular pathways, although it is the extracellular effect that appears to have a primary role in S1P-evoked cell motility. This activation of cell motility is inhibited by an E3-targeted anti-TRPC5 antibody, by the TRPC5 blocker 2-APB, or by a TRPC5 ion-pore mutant. Thus, TRPC5 participates in the signaling underlying cell motility, which plays a central role in the formation and adaption of new arteries and veins and in the progression of vascular disease.

Stretch activation of TRPC5 suggests a physiological role for this channel in mechanotransduction (Gomis et al. 2008 and later studies). Pulmonary neuroepithelial bodies (NEBs) make contact with an important part of the myelinated vagal airway afferents and they can be activated by physiological hyposmotic stimulation through TRPC5. Activation of TRPC5 evokes an increase in intracellular calcium and calcium-dependent exocytosis of ATP, indicating a potential role for NEBs as mechanotransducers of information from the airways to the central nervous system through the TRPC5 channel (Lembrechts et al. 2012). More recently, it was proposed that TRPC5 is a pressure transducer in the baroreceptor neurons and that it therefore plays an important role in maintaining blood pressure stability. This assumption arose from studies on TRPC5−/− mice which experience a decrease in the pressure-elicited activation of the aortic depressor nerve and in the activity of the carotid sinus nerve, as well as an attenuation of the baroreflex-mediated heart response and instability in daily blood pressure (Lau et al. 2016).

As mentioned above, TRPC5 is activated by rTRX and the high concentrations of TRX in rheumatoid arthritis (RA) may reflect an important role for TRPC5 in this disease. TRPC5 and TRPC1 are expressed in secretory fibroblast-like synoviocytes from patients with RA, and TRX, which can be reduced by thioredoxin reductase in joints, has been detected in the serum and synovial fluid from patients with RA. Thus, TRPC5 may represent the link between TRX and cell behavior (Xu et al. 2008).

A challenging role for TRPC5 in cancer therapy and diagnosis has also been proposed. Calcium permeable channels have been suggested as a target for therapy and among them, TRPC5 and TRPC4 may play a role in drug resistance, transmission of drug resistance through extracellular vesicles, tumor vascularization, and evoked cancer cell death. Specifically TRPC5 has been associated to angiogenesis, multidrug resistance in breast and colorectal cancer, and renal cancer cell death. However, these suppositions must be treated with caution as very few studies have been performed on human cancer tissue (reviewed in Gaunt et al. 2016).

Finally, different studies have suggested the possible involvement of TRPC5 in mental retardation, cardiomyopathy, and infantile hypertrophic pyloric stenosis (reviewed in Zholos 2014). A summary of the proposed functional implications of TRPC5 is shown in Fig. 3.
Transient Receptor Potential Cation Channel Subfamily C Member 5, Fig. 3

The diverse roles of TRPC5 in different tissues and systems, and its potential implication in different diseases


TRPC5 is a nonselective cation channel of the “canonical” TRP (TRPC) subfamily that is expressed strongly in the central and peripheral nervous systems and more weakly in many other tissues. Like other TRP channels, TRPC5 is activated by multiple signaling molecules, compounds, and physical stimuli. Less is known about the potent and selective blockers of TRPC5, which will allow the physiological roles of TRPC5 to be better understood. TRPC5 knockout mice are viable with an apparently normal phenotype, although several functions in the brain and vascular system are altered. Nevertheless, and considering the similarities with other TRPC channels that might provoke functional compensation during development, new specific blockers and agonists will be very useful to study the physiological function of TRPC5 or for the treatment of certain diseases.


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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Instituto de NeurocienciasUniversidad Miguel Hernández-CSICAlicanteSpain