FIG. 8.
Potential interplay between ROS/NO production and ion channel modulation in mechanotransduction cascades. In this working model, altered shear stress induced by decrease of flow could be sensed by caveolae, leading to KATP channel inhibition. Closure of KATP channel depolarizes the cell membrane, triggering a variety of downstream events including the activation of eNOS and NOX, generating NO and ROS, respectively. Here, we propose that the production of NO and ROS in these signaling cascades may in turn modulate ion channels including KATP channels, VGCC, and other channels via S-glutathionylation and/or S-nitrosylation, forming a feedback loop in mechanotransduction cascades. Note that the NO and ROS signaling pathways may also have extensive crosstalk, which are outlined in the main text. PI3K, phosphatidyl inositol-3 kinase; Akt, protein kinase B; Prdx6, peroxiredoxin 6; PLA2, phospholipase A2; ROS, reactive oxygen species; NOX, NADPH oxidase; VGCC, voltage-gated calcium channel.