Short transient receptor potential channel 6 (TRPC6) (TRPC6)

Short transient receptor potential channel 6 (TRPC6) is a non-selective cation channel belonging to the canonical TRP family, primarily mediating the influx of calcium (Ca2+) and sodium (Na+) ions in response to phospholipase C-coupled receptor activation [UniProt: Q9Y210]. It is uniquely activated by diacylglycerol (DAG) in a protein kinase C-independent manner, playing a pivotal role in intracellular calcium signaling [PubMed: 10391241]. In the renal system, TRPC6 is localized to the slit diaphragm of podocytes, where it regulates the actin cytoskeleton and maintains the glomerular filtration barrier [PubMed: 15965463]. Gain-of-function mutations in the TRPC6 gene are a known cause of hereditary focal segmental glomerulosclerosis (FSGS), leading to podocyte injury and proteinuria [PubMed: 15965464]. Beyond the kidney, TRPC6 is involved in regulating pulmonary vascular resistance and neuronal development in the hippocampus [PubMed: 29138241]. Consequently, TRPC6 has emerged as a significant therapeutic target for chronic kidney diseases and pulmonary arterial hypertension, with several small-molecule inhibitors currently in clinical and preclinical development [ClinicalTrials.gov: NCT04176536]. Therapeutic modulation of TRPC6 aims to restore calcium homeostasis and prevent tissue remodeling in high-stress physiological environments.

Other names

Transient receptor potential cation channel subfamily C member 6TRP-6FSGS2Transient receptor potential channel 6

TRPC6 inhibitors act by binding to the channel pore or allosteric sites to prevent the influx of calcium and sodium ions, thereby mitigating pathological calcium signaling that leads to podocyte detachment in the kidney or excessive contraction in pulmonary vasculature [PubMed: 32814718].