A slit diaphragm mechanosensor protein podocin may regulate the mechanical potentiation of receptor-activated TRPC6 channel

Jun Ichikawa, Midori Nakagawa, Ryuji Inoue
2019 Proceedings for Annual Meeting of The Japanese Pharmacological Society  
It has been suggested that excessive activities or focal segmental glomerulosclerosis (FSGS)-associated gain-offunction mutations of the canonical transient receptor potential 6 (TRPC6) channel may result in a proteinuria and progressive kidney failure. In this study, we investigated the impact of podocin, a mechanosensor at the slit diaphragm of glomerulus, on these enhanced channel activities by Ca 2+ imaging and patch clamp techniques. Co-expression of podocin suppressed
more » ... responses of receptor-activated wild-type and 131T-FSGS mutant of TRPC6 channels overexpressed in HEK293 cells. In differentiated cultured podocytes (MPCs) stably overexpressing TRPC6, its mechanical potentiation after receptor activation was found to be decreased as compared with that observed in the heterologous system. However, this decrease was reversed by siRNA knockdown of endogenous podocin expression. These results suggest that the mechanosensitivity of receptor-activated TRPC6 channel may be negatively regulated by interaction with podocin, the mechanism being presumably important to normalize otherwise exaggerated TRPC6-mediated Ca 2+ responses. Poster Sessions
doi:10.1254/jpssuppl.92.0_2-p-105 fatcat:5g2praypvrh2rew64y4srqyv7q