KATP channels are an important component of the shear-sensing mechanism in the pulmonary microvasculature. 
To investigate the role of a KATP channel in sensing shear, specifically its cessation, in the endothelial cells of the pulmonary microvasculature.  Endothelial cells isolated from the pulmonary microvasculature of wild-type and KATP channel knockout (KIR6.2-/-) mice were either statically cultured (non-flow-adapted) or kept under flow (flow-adapted) and the KIR currents in these cells were monitored by whole-cell patch-clamp technique during flow and its cessation.  Membrane potential changes, generation of reactive oxygen species (ROS), and Ca2+ influx with flow cessation were evaluated by the use of fluorescent dyes.  Lungs isolated from wild-type mice were imaged to visualize ROS generation in the subpleural endothelium.  By patch-clamp analysis, reduction in the KIR current with cessation of flow occurred only in wild-type cells that were flow-adapted and not in flow-adapted KIR6.2-/- cells.  Similar observations were made using changes in bisoxonol fluorescence as an index of cell membrane potential.  Generation of ROS and Ca2+ influx that follow membrane depolarization were significantly lower in statically cultured and in KIR6.2-/- cells as compared to flow-adapted wild-type cells.  Imaging of subpleural endothelial cells of the whole lung showed that the KATP antagonist glyburide caused the production of ROS in the absence of flow cessation.  The responses to stop of flow (viz.  membrane depolarization, KIR currents, ROS, Ca2+) were significantly altered with knockout of KATP channels, which indicates that this channel is an important component of the pulmonary endothelial response to abrupt loss of shear stress.