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Transient receptor potential cation channel subfamily C member 3, Transient receptor potential cation channel subfamily C member 6, Transient receptor potential cation channel subfamily C member 7 (TRPC3, TRPC6, TRPC7)

Target
TRPC3, TRPC6, TRPC7
Molecular classification
Ion channel, Cation channel, Transient receptor potential channel, Membrane protein
01

Overview

The transient receptor potential cation channel subfamily C members 3, 6, and 7 (TRPC3, TRPC6, TRPC7) are non-selective calcium-permeable cation channels belonging to the TRPC superfamily. They share high sequence and structural similarity, each forming tetrameric channel complexes in the plasma membrane. Activation typically occurs via diacylglycerol in the phospholipase C signaling pathway, making them important effectors of G protein-coupled and tyrosine kinase receptor signaling. These channels regulate calcium influx into excitable and non-excitable cells and are key in vascular, neuronal, and kidney physiology. Dysregulation or mutation of these channels, particularly TRPC6, is implicated in diseases including cardiac hypertrophy, glomerular kidney disease, and certain neurological disorders. Their redundancy and overlapping expression create challenges for selective drug development and for dissecting their specific physiological roles[2][5][6][7].

Other names
TRP-3TRP-6TRP-7TRPC3/6/7 subfamilycanonical TRP channels
02

Mechanism of action

Channel blockers/inhibitors: Inhibit ion flow through the channel, reducing pathologic Ca²⁺ influx Modulators: Modulate channel gating, influence receptor-activated cellular responses

03

Biological functions

Calcium entry and signalingReceptor-activated cation influxMechanosensationSignal transduction via phospholipase C-coupled (PLC-coupled) receptor pathwaysRegulation of vascular tone, neuronal excitability, and other cell signaling events
04

Disease associations

Cardiovascular disease (e.g., hypertension, cardiac hypertrophy, heart failure)Kidney diseases (e.g., focal segmental glomerulosclerosis—TRPC6)Neurological disorders or neurodegenerationHearing and sensory deficitsPotential roles in inflammation and cancer (less established)
05

Safety considerations

Off-target effects due to channel redundancy (especially, TRPC3 and TRPC6 have overlapping function)Broad tissue distribution increases risk of side effects (e.g., altered vascular tone, CNS effects)Potential compensatory mechanisms leading to reduced efficacy or unexpected outcomes
06

Interacting drugs

SAR7334

4 more in the full profile.

07

Biomarkers

Elevated TRPC6 expression as a biomarker in certain kidney diseasesTRPC3/6 activity or expression may serve as functional biomarkers in cardiovascular disease and neurodegeneration, but not firmly established for clinical practice

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