Protein Kinase G Inhibits Flow-Induced Ca2+ Entry into Collecting Duct Cells

Abstract

The renal cortical collecting duct (CCD) into collecting duct cells. Furthermore, substances such as atrial natriuretic peptide and nitric oxide, which increase cGMP, abrogate flow-induced Ca 2+ entry through PKG-mediated inhibition of these channels.

Nitric Oxide–Dependent Feedback Loop Regulates Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Cooperativity and Endothelial Function in Small Pulmonary Arteries

“…In this context, a dual role for NO—as a mediator of TRPV4‐vasodilation and as a limiter of TRPV4 channel activity—provides a more precise control over channel activation and vasodilation. Prior studies in the expression systems reveal 2 possibilities for the modulation of TRPV4 channel function by NO: an increase in channel activity by S ‐nitrosylation,18 and a decrease in channel activity by GC‐PKG signaling 19. Although S ‐nitrosylation and activation of TRPV4 channels by NO cannot be ruled out, our results suggest that NO‐induced TRPV4 channel inhibition via GC‐PKG pathway predominates in intact PAs.…”

“…Studies in expression systems reveal an increase in the activity of TRPV4 channels by S ‐nitrosylation18 and a decrease by GC‐PKG signaling,19 and NO can activate both these mechanisms. We hypothesized that NO released by TRPV4‐eNOS signaling serves as an immediate feedback regulator of TRPV4 channel activity in small PAs.…”

“…In cultured cells, S ‐nitrosylation of TRPV4 channels increased the channel function,18 and activation of GC‐PKG signaling reduced the channel activity 19. Therefore in PAs, TRPV4‐eNOS signaling could activate a bidirectional regulation, where TRPV4 channels promote NO release, which in turn regulates TRPV4 channel function.…”

Discrete Control of TRPV4 Channel Function in the Distal Nephron by Protein Kinases A and C

“…Several reports have demonstrated that TRPV4 can physically interact with TRPP2 (also known as polycystin-2) in distal nephron cells to form mechanosensitive heteromeric complexes (16,17). TRPV4 activity is drastically impaired in cyst cells from PCK453 rats, an animal model of autosomal recessive polycystic kidney disease (ARPKD), which is causative for the inability to increase [Ca 2ϩ ] i in response to elevated flow (18).…”

“…Recent evidence suggested that cGMP can act through PKG to inhibit flow-induced increases in [Ca 2ϩ ] i in cultured M1 collecting duct cells (17). However, the cGMP/PKG pathway has no direct inhibitory actions on TRPV4, but it acts on its heteromeric counterpart, TRPP2 (17).…”