Short transient receptor potential channel 3 (TrpC3) also known as transient receptor protein 3 (TRP-3) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the TRPC3

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. The TRPC3/6/7 subfamily are implicated in the regulation of vascular tone, cell growth, proliferation and pathological hypertrophy. These are diacylgylcerol-sensitive cation channels known regulate intracellular calcium via activation of the phospholipase C (PLC) pathway and/or by sensing Ca2+ store depletion. Together, their role in calcium homeostasis has made them potential therapeutic targets for a variety of central and peripheral pathologies.

Function

Non-specific cation conductance elicited by the activation of

TrkB Tropomyosin receptor kinase B (TrkB), also known as tyrosine receptor kinase B, or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the ''NTRK2'' gene. TrkB is a recepto ...

BDNF Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the cano ...

is TRPC3-dependent in the CNS. TRPC channels are almost always co-localized with

mGluR1 The glutamate receptor, metabotropic 1, also known as GRM1, is a human gene which encodes the metabotropic glutamate receptor 1 (mGluR1) protein. Function L-glutamate is the major excitatory neurotransmitter in the central nervous system and ...

-expressing cells and likely play a role in mGluR-mediated EPSPs. The TRPC3 channel has been shown to be preferentially expressed in non-excitable cell types, such as

oligodendrocyte Oligodendrocytes (), or oligodendroglia, are a type of neuroglia whose main functions are to provide support and insulation to axons in the central nervous system of jawed vertebrates, equivalent to the function performed by Schwann cells in the ...

s. However, evidence suggests that active TRPC3 channels in basal ganglia (BG) output neurons are responsible for maintaining a tonic inward depolarizing current that regulates resting membrane potential and promotes regular neuronal firing. Conversely, inhibiting TRPC3 promotes cellular hyperpolarization, which can lead to slower and more irregular neuronal firing. While it's unclear if TRPC3 channels have equal expression, other members of the TRPC family have been localized to the

axon hillock The axon hillock is a specialized part of the cell body (or soma) of a neuron that connects to the axon. It can be identified using light microscopy from its appearance and location in a neuron and from its sparse distribution of Nissl substance. ...

, cell body, and dendritic processes of dopamine-expressing cells. The neuromodulator,

substance P Substance P (SP) is an undecapeptide (a peptide composed of a chain of 11 amino acid residues) and a member of the tachykinin neuropeptide family. It is a neuropeptide, acting as a neurotransmitter and as a neuromodulator. Substance P and its clos ...

, activates TRPC3/7 channels inducing cellular currents that underlie rhythmic pacemaker activity in the

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...

, enhancing the regularity and frequency of respiratory rhythms, showing homology to the mechanism described in BG neurons. Transgenic cardiomyocytes expressing TRPC3 show prolonged action potential duration when exposed to a TRPC3 agonist. The same cardiomyocytes also increase their firing rate with agonist exposure under a current-clamp tetanus protocol suggesting that they may play a role in cardiac arrhythmogenesis.

Modulators

A small molecule agonist is

GSK1702934A GSK1702934A is a chemical compound which acts as an activator of the TRPC family of calcium channels, with selectivity for the TRPC3 and TRPC6 Transient receptor potential cation channel, subfamily C, member 6, also known as TRPC6, is a human ge ...

and antagonists are

GSK417651A GSK417651A is a chemical compound which acts as a blocker of the TRPC family of calcium channels, with selectivity for the TRPC3 and TRPC6 Transient receptor potential cation channel, subfamily C, member 6, also known as TRPC6, is a human gene ...

and GSK2293017A. A commercially available inhibitor is available in the form of a pyrazole compound, Pyr3 TRPC3 has been shown to specifically

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with

TRPC1 Transient receptor potential canonical 1 (TRPC1) is a protein that in humans is encoded by the ''TRPC1'' gene. Function TRPC1 is an ion channel located on the plasma membrane of numerous human and animal cell types. It is a nonspecific cation ...

and

TRPC6 Transient receptor potential cation channel, subfamily C, member 6, also known as TRPC6, is a human gene encoding a protein of the same name. TRPC6 is a transient receptor potential channel of the classical TRPC subfamily. It has been associated w ...

References

External links

* Ion channels {{membrane-protein-stub

Function

Modulators

See also

References

Further reading

External links