TRPC Related Drug Discovery Products

The TRPC subfamily of TRP channels is distinct from other TRP channel subfamilies in that its members participate in the so-called slow sustained mode of Ca²⁺ signaling, which necessitates prolonged elevations of intracellular Ca²⁺ ([Ca²⁺]i), in addition to being responsible for agonist-activated nonselective cation currents. Contrary to the TRPC-mediated nonselective cation current, which requires activation of a G protein-coupled receptor (GPCR)-Gq-PLCβ signaling pathway in order to stimulate cells, SOCE (store operated calcium entry) and Icrac can be activated passively by depletion of the internal Ca²⁺ stores.

Fig.1 The physiological and pathophysiological roles of TRPC channels.^1,2

Creative Biolabs can offer TRPC in vitro assays and related products with the best quality:

• TRPC Assays
• Ion Channel Cell Lines
• Ion Channel Membranes
• Membrane Protein Tools

Overview of TRPC

• Activation by Phospholipase C

Moves that activate the IP3 receptor by activating phospholipase C through the GPCR/Gq pathway also invariably activate TRPC channels. In that both depend on PLC activation, vertebrate TRPC activation is similar to Drosophila Trp and Trp-like activation. But it is unknown how PLC activation triggers the activation of either TRPCs or invertebrate Trp channels.

• Conformational Coupling

Studies revealed that the activation of TRPCs may include IP3 receptors. In agreement with these findings and the hypothesis that activation of IP3Rs may lead to a conformational coupling between IP3R and TRPCs with attendant activation of the TRPC channel, the type II IP3R and TRPC1 were shown to coprecipitate from lysates of human platelets that had been prestimulated with either a receptor agonist, thrombin, that activates the GPCR-Gq-PLC pathway or by a maneuver that promotes store depletion.

• Diacylglycerol (DAG) and Lysophosphatidylcholine (LysoPC)

Along with IP3, DAG is the additional product produced when PLCs are activated. In cells expressing cloned TRPC3, actions leading to DAG formation in response to agonist stimulation of the GPCR-Gq-PLC pathway fail to activate TRPC3 under conditions that permit activation of the same TRPC3 by exogenous OAG under ionic conditions that permit differentiation of transfected TRPC3 from endogenous TRPCs. Contrarily, transfected TRPC3, C6, and C7 are activated by the addition of exogenous OAG, whereas HEK 293 cells do not respond to exogenous OAG with Ca²⁺ influx despite expressing TRPC3 and TRPC6, and vice versa. Lysophosphatidylcholine (LysoPC), which stimulates TRPC5, is the second lipid found to activate a TRPC. It has not yet been determined whether it affects other TRPCs.

References

1. Chen, Xingjuan, et al. "Transient receptor potential canonical (TRPC) channels: then and now." Cells 9.9 (2020): 1983.
2. Image retrieved from Figure 7 " The physiological and pathophysiological roles of TRPC channels. " Chen, et al. 2020, used under CC BY 4.0. The original image was modified by extracting and the title was changed to " The physiological and pathophysiological roles of TRPC channels.".