| First Author | Chatterjee S | Year | 2006 |
| Journal | Microcirculation | Volume | 13 |
| Issue | 8 | Pages | 633-44 |
| PubMed ID | 17085424 | Mgi Jnum | J:135920 |
| Mgi Id | MGI:3794803 | Doi | 10.1080/10739680600930255 |
| Citation | Chatterjee S, et al. (2006) KATP channels are an important component of the shear-sensing mechanism in the pulmonary microvasculature. Microcirculation 13(8):633-44 |
| abstractText | OBJECTIVE: To investigate the role of a KATP channel in sensing shear, specifically its cessation, in the endothelial cells of the pulmonary microvasculature. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. |
