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Microcirculation. 2006 Dec;13(8):633-44.

KATP channels are an important component of the shear-sensing mechanism in the pulmonary microvasculature.

Author information

1
Institute for Environmental Medicine, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104-6068, USA.

Abstract

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.

PMID:
17085424
DOI:
10.1080/10739680600930255
[Indexed for MEDLINE]
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