TRPC Assays
Background of TRPC
The TRPC family is the closest homolog to Drosophila TRP channels. The TRPC family consists of seven members (TRPC1-7) with trpc2 being a pseudogene in human beings. The seven mammalian homologs share 30% amino acid identity within the N-terminal 750 900 amino acids. Based on sequence alignments and functional comparisons, the mammalian TRPCs fall into four subsets: TRPC1, TRPC2, TRPC3/6/7, and TRPC4/5.
Fig. 1. Structure of Transient receptor potential canonical 4 (TRPC4). (Wang, 2020)
Subtypes and Mechanisms of TRPC
- TRPC1
TRPC1 is activated by the hormone, orexin-A, which is associated with the regulation of sleep/wake-up states, alertness, and appetite. As expressed broadly, the TRPC1 channel is related to many physiological functions.
- TRPC2
The TRPC2 is a pseudogene in humans; however, in rodents, it plays an important role in pheromone detection via the vomeronasal sensory neurons (VSN). In these cells, the TRPC2 protein is mainly localized to the sensory microvilli, which are specialized for chemical signal detection. In the acrosome region of sperm, TRPC2 was also detected, which indicated its possible role in fertilization.
TRPC3 is most prominently expressed in specific regions of the brain, the heart, and the lungs. TRPC3 is a constitutively active receptor-operated channel that can be further stimulated by DAG. TRPC3 is a multifunctional cellular sensor with a wide range of physiological/pathological functions.
- TRPC4
TRPC4 has been shown to be involved in response to neural injury, the regulation of neurite outgrowth, and neuronal exocytosis. In human kidney epithelial cells, silencing TRPC4 impairs the secretion of thrombopsondin-1 (TSP1).
TRPC5 is mainly expressed in brain tissue, especially in the fetal brain, indicating that TRPC5 may play an important role during brain development. TRPC5 participates in the formation of transient working memory in the entorhinal cortex. TRPC5 is important for amygdala function and fear-related behavior.
TRPC6 has been reported to play an important role in brain development and diseases. Its physiological function is involved with excitatory synapse formation, dendritic outgrowth, and BDNF-mediated survival of granule cells in the cerebellum. TRPC6 also participates in many pathological processes, including neuronal damage in stroke, Aβ-production in Alzheimer's Disease (AD), and human glioma cell proliferation.
TRPC7 is mainly expressed in the kidney and pituitary gland and is closely related to TRPC6. TRPC7 is a receptor-activated channel activated by the PLC-mediated metabolism of PIP2 and production of DAG.
Assay List of TRPC Channels
Creative Biolabs can provide a range of assays of TRPC channels. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | Depression-like behavior associated with E/I imbalance of mPFC and amygdala without TRPC channels in mice of knockout IL-10 from microglia |
| Journal | Brain Behav Immun |
| Published | 2021 |
| Abstract | Depression is critical to public health, as it is associated with a huge loss of quality of life. Mood disorders, including increased levels of circulating biomarkers for inflammation, are commonly associated with changes in the immune system. Interleukin-10 (IL-10) is a key cytokine that inhibits excessive inflammatory responses and is related to the anti-inflammatory and protective functions of the central nervous system (CNS). There is extensive evidence that IL-10 plays a crucial role in the progression of depression. There is a complex network relationship between TRPC subtypes and cytokines in specific states. Recombinant IL-10 results in the attenuation of N-cadherin expression, which interacts with TRPC4 and TRPC6 during stress fiber formation. IL-10 is produced through the independent B cell receptor pathway, which depends on the upregulation of the TRPC1 protein. Altered TRPC expression has been implicated in emotional disorders. Microglia-derived IL-10 plays a role in both the immune balance and emotional response. Cx3cr1CreERIL-10-/- mice were used in this study, where researchers aimed to identify the role of IL-10 from microglia in depression and anxiety-like behavior and to explore the relationship between this process and TRPC channel proteins. |
| Result | Results showed enhanced depression and anxiety-like behavior in the Cx3cr1CreERIL-10-/- mice, which may be related to an imbalance in local excitatory and inhibitory transmission, as well as neuroinflammation in the mPFC and amygdala. This imbalance was associated with increased local inflammation. Although many studies have demonstrated the role of TRPC channels in emotional responses, this study shows that TRPC is not involved in this process in Cx3cr1CreERIL-10-/- mice. Further studies are needed to elucidate the molecular mechanism of the emotional changes in Cx3cr1CreERIL-10-/- mice and the possible contribution of this kind of cytokine in the pathologic state. This study focused on the microglia-targeted production of IL-10. |
References
- Wang, H.; et al. TRPC channels: Structure, function, regulation and recent advances in small molecular probes. Pharmacol Ther. 2020, 209: 107497.
- Yang, L.; et al. Depression-like behavior associated with E/I imbalance of mPFC and amygdala without TRPC channels in mice of knockout IL-10 from microglia. Brain, Behavior, and Immunity. 2021, 97: 68-78.
