Transient receptor potential cation channel subfamily C member 4 and 5 (TRPC4/5) (TRPC4/5)

Transient receptor potential canonical 4 and 5 (TRPC4/5) are non-selective cation channels that function as homotetramers or heterotetramers to regulate the influx of calcium and sodium ions [1, 8]. These channels are primarily activated through G-protein coupled receptor (GPCR) signaling pathways involving Gq/11 or Gi/o proteins and phospholipase C [8, 16]. In the central nervous system, TRPC4/5 channels are highly expressed in the amygdala and prefrontal cortex, where they modulate neuronal excitability and are implicated in the pathophysiology of anxiety and depression [4, 9, 11]. In the periphery, TRPC5 is a critical driver of podocyte injury in the kidney via the TRPC5-Rac1 pathway, making it a target for treating proteinuric kidney diseases like focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy [3, 6, 13]. Pharmacological inhibition of these channels using small molecules like GFB-887 and BI 1358894 has shown promise in clinical trials for kidney and psychiatric disorders, respectively [7, 9, 18]. Additionally, TRPC4/5 channels are being investigated for their roles in chronic pain and cancer drug resistance [1, 15, 16].

Other names

TRPC4-TRPC5 heteromerTRPC4/C5Transient receptor potential cation channel subfamily C member 4 and 5TRPC1/4/5 complex

Inhibition of TRPC4/5 cation channels to modulate calcium signaling, specifically targeting the TRPC5-Rac1 pathway in kidney podocytes and neuronal excitability in the amygdala [3, 4, 13].