P-Glycoprotein Contributes to Cell Membrane Depolarization of Hippocampus and Neocortex in a Model of Repetitive Seizures Induced by Pentylenetetrazole in Rats

2013 ◽  
Vol 19 (38) ◽  
pp. 6732-6738 ◽  
Author(s):  
Jerónimo A. Auzmendi ◽  
Sandra Orozco-Suárez ◽  
Ivette Bañuelos-Cabrera ◽  
María Eva González-Trujano ◽  
Eduardo Calixto González ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Membrane Depolarization ◽  
P Glycoprotein

scholarly journals Activation of endothelial NADPH oxidase during normoxic lung ischemia is KATP channel dependent

2005 ◽  
Vol 289 (6) ◽  
pp. L954-L961 ◽  
Author(s):  
Qunwei Zhang ◽  
Ikuo Matsuzaki ◽  
Shampa Chatterjee ◽  
Aron B. Fisher
Keyword(s):  
Endothelial Cells ◽  
Membrane Potential ◽  
Endothelial Cell ◽  
Cell Membrane ◽  
Nadph Oxidase ◽  
Membrane Depolarization ◽  
Fluorescence Probes ◽  
Ros Generation ◽  
Wild Type ◽  
Channel Dependent

Previous studies have shown endothelial cell membrane depolarization and generation of reactive oxygen species (ROS) in endothelial cells with abrupt reduction in shear stress (ischemia). This study evaluated the role of ATP-sensitive potassium (KATP) channels and NADPH oxidase in the ischemic response by using Kir6.2−/− and gp91phox−/− mice. To evaluate ROS generation, we subjected isolated perfused mouse lungs labeled with 2′,7′-dichlorodihydrofluorescein (DCF), hydroethidine (HE), or diphenyl-1-pyrenylphosphine (DPPP) to control perfusion followed by global ischemia. In wild-type C57BL/6J mice, imaging of subpleural endothelial cells showed a time-dependent increase in intensity for all three fluorescence probes with ischemia, which was blocked by preperfusion with cromakalim (a KATP channel agonist) or diphenyleneiodonium (DPI, a flavoprotein inhibitor). Endothelial cell fluorescence with bis-oxonol, a membrane potential probe, increased during lung ischemia indicating cell membrane depolarization. The change in membrane potential with ischemia in lungs of gp91phox−/− mice was similar to wild type, but ROS generation did not occur. Lungs from Kir6.2−/− showed marked attenuation of the change in both membrane potential and ROS production. Thus membrane depolarization during lung ischemia requires the presence of a KATP channel and is required for activation of NADPH oxidase and endothelial ROS generation.

scholarly journals Membrane depolarization is the trigger for PI3K/Akt activation and leads to the generation of ROS

2012 ◽  
Vol 302 (1) ◽  
pp. H105-H114 ◽  
Author(s):  
Shampa Chatterjee ◽  
Elizabeth A. Browning ◽  
NanKang Hong ◽  
Kris DeBolt ◽  
Elena M. Sorokina ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Membrane ◽  
Fluid Shear Stress ◽  
Membrane Depolarization ◽  
Microvascular Endothelial Cells ◽  
Ros Generation ◽  
Ros Production ◽  
Akt Activation ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Microvascular Endothelial

Loss of fluid shear stress (ischemia) to the lung endothelium causes endothelial plasma membrane depolarization via ATP-sensitive K+(KATP) channel closure, initiating a signaling cascade that leads to NADPH oxidase (NOX2) activation and ROS production. Since wortmannin treatment significantly reduces ROS production with ischemia, we investigated the role of phosphoinositide 3-kinase (PI3K) in shear-associated signaling. Pulmonary microvascular endothelial cells in perfused lungs subjected to abrupt stop of flow showed membrane depolarization and ROS generation. Stop of flow in flow-adapted mouse pulmonary microvascular endothelial cells in vitro resulted in the activation of PI3K and Akt as well as ROS generation. ROS generation in the lungs in situ was almost abolished by the PI3K inhibitor wortmannin and the PKC inhibitor H7. The combination of the two (wortmannin and H7) did not have a greater effect. Activation of NOX2 was greatly diminished by wortmannin, knockout of Akt1, or dominant negative PI3K, whereas membrane depolarization was unaffected. Ischemia-induced Akt activation (phosphorylation) was not observed with KATPchannel-null cells, which showed minimal changes in membrane potential with ischemia. Activation of Akt was similar to wild-type cells in NOX2-null cells, which do not generate ROS with ischemia. Cromakalim, a KATPchannel agonist, prevented both membrane depolarization and Akt phosphorylation with ischemia. Thus, Akt1 phosphorylation follows cell membrane depolarization and precedes the activation of NOX2. These results indicate that PI3K/Akt and PKC serve as mediators between endothelial cell membrane depolarization and NOX2 assembly.

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