TRPC6
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| Location (UCSC) | Chr 11: 101.45 – 101.87 Mb | Chr 9: 8.54 – 8.68 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Transient receptor potential cation channel, subfamily C, member 6 or Transient receptor potential canonical 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.[5]
TRPC6 channels are nonselective cation channels that respond directly to diacylglycerol (DAG), a product of phospholipase C activity. This activation leads to cellular depolarization and calcium influx.[5][6]
Unlike the closely related TRPC3 channels, TRPC6 channels possess the distinctive ability to transport heavy metal ions. TRPC6 channels facilitate the transport of zinc ions, promoting their accumulation inside cells.[6][7] In addition, despite their non-selectiveness, TRPC6 exhibits a strong preference for calcium ions, with a permeability ratio of calcium to sodium (PCa/PNa) of roughly six. This selectivity is significantly higher compared to TRPC3, which displays a weaker preference for calcium with a (PCa/PNa) ratio of only 1.1.[6]
Function
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TRPC6 channels are widely distributed in the human body and are emerging as crucial regulators of several key physiological functions:
In blood vessels
Small arteries and
TRPC6 channels are present both in endothelial and smooth muscle cells[8] and their function is similar to α‑adrenoreceptors; they are both involved in vasoconstriction.[9] However, TPRC6-mediated vasoconstriction is mechanosensetive (i.e. activated by mechanical stimulation) and these channels are involved in maintenance of the myogenic tone of blood vessels and autoregulation of blood flow.[8]
When intravascular blood pressure rises, this causes stretching of the walls of blood vessels. This mechanical stretch activates the TRPC6 channel. Once activated, TRPC6 allows Ca2+ to enter the smooth muscle cells. This increase in intracellular Ca2+ triggers a chain reaction leading to vasoconstriction.[6]
In the central nervous system
Research of learning and memory mechanisms suggests that a continuous increase in the strength of synaptic transmission is necessary to achieve long-term modification of neural network properties and memory storage. TRPC6 appears to be essential for the formation of an excitatory synapse; overexpressing TRPC6 greatly increased dendritic spine density and the level of synapsin I and PSD-95 cluster, known as the pre- and postsynaptic markers.[10]
TRPC6 has also been proven to participate in neuroprotection and its neuroprotective effect could be explained due to the antagonism of extrasynaptic NMDA receptor (NMDAR)-mediated intracellular calcium overload. TRPC6 activates calcineurin, which impedes the NMDAR activity.[10]
Hyperactivation of NMDAR is a critical event in
In the kidneys
TRPC6 channels are extensively present throughout the kidney, both in the
Clinical significance
Since TRPC6 channels play a multifaceted role by participating in various signaling pathways, these channels are emerging as key players in the pathogenesis of a wide range of diseases including:[14]
- Kidney diseases
- Disorders of the nervous system
- Autism spectrum disorders
- Brain ischemia
- Cancers
- Cardiovascular diseases
- Pulmonary diseases
- Lung fibrosis
Interactions
TRPC6 has been shown to
Ligands
Two of the primary
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000137672 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031997 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ PMID 29700422.
- ^ PMID 24756706.
- PMID 36289215.
- ^ PMID 18215190.
- ^ PMID 35371476.
- ^ license.
- PMID 15924139.
- ^ PMID 26385481.
- PMID 34179830.
- PMID 37072606.
- PMID 14761972.
- PMID 14699131.
- PMID 12032305.
- S2CID 21872392.
- ^ PMID 9718074.
- S2CID 14097884.
- PMID 25511254.
Further reading
- Heiner I, Eisfeld J, Lückhoff A (2004). "Role and regulation of TRP channels in neutrophil granulocytes". Cell Calcium. 33 (5–6): 533–40. PMID 12765698.
- Walz G (September 2005). "Slit or pore? A mutation of the ion channel TRPC6 causes FSGS". Nephrology, Dialysis, Transplantation. 20 (9): 1777–9. PMID 15998650.
- Clapham DE, Julius D, Montell C, Schultz G (December 2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacological Reviews. 57 (4): 427–50. S2CID 17936350.
- Schlöndorff JS, Pollak MR (December 2006). "TRPC6 in glomerular health and disease: what we know and what we believe". Seminars in Cell & Developmental Biology. 17 (6): 667–74. PMID 17116414.
- Dietrich A, Gudermann T (2007). "TRPC6". Transient Receptor Potential (TRP) Channels. Handbook of Experimental Pharmacology. Vol. 179. pp. 125–41. PMID 17217054.
External links
- TRPC6+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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