The Experts below are selected from a list of 276 Experts worldwide ranked by ideXlab platform
Jason X.-j. Yuan - One of the best experts on this subject based on the ideXlab platform.
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Augmented K(+) currents and mitochondrial Membrane Depolarization in pulmonary artery myocyte apoptosis.
American journal of physiology. Lung cellular and molecular physiology, 2001Co-Authors: Stefanie Krick, Oleksandr Platoshyn, Sharon S. Mcdaniel, Lewis J. Rubin, Jason X.-j. YuanAbstract:The balance between apoptosis and proliferation in pulmonary artery smooth muscle cells (PASMCs) is important in maintaining normal pulmonary vascular structure. Activity of voltage-gated K(+) (K(V)) channels has been demonstrated to regulate cell apoptosis and proliferation. Treatment of PASMCs with staurosporine (ST) induced apoptosis in PASMCs, augmented K(V) current [I(K(V))], and induced mitochondrial Membrane Depolarization. High K(+) (40 mM) negligibly affected the ST-induced mitochondrial Membrane Depolarization but inhibited the ST-induced I(K(V)) increase and apoptosis. Blockade of K(V) channels with 4-aminopyridine diminished I(K(V)) and markedly decreased the ST-mediated apoptosis. Furthermore, the ST-induced apoptosis was preceded by the increase in I(K(V)). These results indicate that ST induces PASMC apoptosis by activation of plasmalemmal K(V) channels and mitochondrial Membrane Depolarization. The increased I(K(V)) would result in an apoptotic volume decrease due to a loss of cytosolic K(+) and induce apoptosis. The mitochondrial Membrane Depolarization would cause cytochrome c release, activate the cytosolic caspases, and induce apoptosis. Inhibition of K(V) channels would thus attenuate PASMC apoptosis.
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augmented k currents and mitochondrial Membrane Depolarization in pulmonary artery myocyte apoptosis
American Journal of Physiology-lung Cellular and Molecular Physiology, 2001Co-Authors: Stefanie Krick, Oleksandr Platoshyn, Sharon S. Mcdaniel, Lewis J. Rubin, Jason X.-j. YuanAbstract:The balance between apoptosis and proliferation in pulmonary artery smooth muscle cells (PASMCs) is important in maintaining normal pulmonary vascular structure. Activity of voltage-gated K(+) (K(V)) channels has been demonstrated to regulate cell apoptosis and proliferation. Treatment of PASMCs with staurosporine (ST) induced apoptosis in PASMCs, augmented K(V) current [I(K(V))], and induced mitochondrial Membrane Depolarization. High K(+) (40 mM) negligibly affected the ST-induced mitochondrial Membrane Depolarization but inhibited the ST-induced I(K(V)) increase and apoptosis. Blockade of K(V) channels with 4-aminopyridine diminished I(K(V)) and markedly decreased the ST-mediated apoptosis. Furthermore, the ST-induced apoptosis was preceded by the increase in I(K(V)). These results indicate that ST induces PASMC apoptosis by activation of plasmalemmal K(V) channels and mitochondrial Membrane Depolarization. The increased I(K(V)) would result in an apoptotic volume decrease due to a loss of cytosolic K(+) and induce apoptosis. The mitochondrial Membrane Depolarization would cause cytochrome c release, activate the cytosolic caspases, and induce apoptosis. Inhibition of K(V) channels would thus attenuate PASMC apoptosis.
Stephen D. Roper - One of the best experts on this subject based on the ideXlab platform.
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Intracellular Ca2+ and TRPM5-mediated Membrane Depolarization produce ATP secretion from taste receptor cells
The Journal of Physiology, 2010Co-Authors: Yijen A. Huang, Stephen D. RoperAbstract:ATP is a transmitter secreted from taste bud receptor (Type II) cells through ATP-permeable gap junction hemichannels most probably composed of pannexin 1. The elevation of intracellular Ca2+ and Membrane Depolarization are both believed to be involved in transmitter secretion from receptor cells, but their specific roles have not been fully elucidated. In the present study, we show that taste-evoked ATP secretion from mouse vallate receptor cells is evoked by the combination of intracellular Ca2+ release and Membrane Depolarization. Unexpectedly, ATP secretion is not blocked by tetrodotoxin, indicating that transmitter release from these cells still takes place in the absence of action potentials. Taste-evoked ATP secretion is absent in receptor cells isolated from TRPM5 knockout mice or in taste cells from wild type mice where current through TRPM5 channels has been eliminated. These findings suggest that Membrane voltage initiated by TRPM5 channels is required for ATP secretion during taste reception. Nonetheless, even in the absence of TRPM5 channel activity, ATP release could be triggered by depolarizing cells with KCl. Collectively, the findings indicate that taste-evoked elevation of intracellular Ca2+ has a dual role: (1) Ca2+ opens TRPM5 channels to depolarize receptor cells and (2) Ca2+ plus Membrane Depolarization opens ATP-permeable gap junction hemichannels.
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Intracellular Ca(2+) and TRPM5-mediated Membrane Depolarization produce ATP secretion from taste receptor cells.
The Journal of physiology, 2010Co-Authors: Yijen A. Huang, Stephen D. RoperAbstract:ATP is a transmitter secreted from taste bud receptor (Type II) cells through ATP-permeable gap junction hemichannels most probably composed of pannexin 1. The elevation of intracellular Ca(2+) and Membrane Depolarization are both believed to be involved in transmitter secretion from receptor cells, but their specific roles have not been fully elucidated. In the present study, we show that taste-evoked ATP secretion from mouse vallate receptor cells is evoked by the combination of intracellular Ca(2+) release and Membrane Depolarization. Unexpectedly, ATP secretion is not blocked by tetrodotoxin, indicating that transmitter release from these cells still takes place in the absence of action potentials. Taste-evoked ATP secretion is absent in receptor cells isolated from TRPM5 knockout mice or in taste cells from wild type mice where current through TRPM5 channels has been eliminated. These findings suggest that Membrane voltage initiated by TRPM5 channels is required for ATP secretion during taste reception. Nonetheless, even in the absence of TRPM5 channel activity, ATP release could be triggered by depolarizing cells with KCl. Collectively, the findings indicate that taste-evoked elevation of intracellular Ca(2+) has a dual role: (1) Ca(2+) opens TRPM5 channels to depolarize receptor cells and (2) Ca(2+) plus Membrane Depolarization opens ATP-permeable gap junction hemichannels.
Stefanie Krick - One of the best experts on this subject based on the ideXlab platform.
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Augmented K(+) currents and mitochondrial Membrane Depolarization in pulmonary artery myocyte apoptosis.
American journal of physiology. Lung cellular and molecular physiology, 2001Co-Authors: Stefanie Krick, Oleksandr Platoshyn, Sharon S. Mcdaniel, Lewis J. Rubin, Jason X.-j. YuanAbstract:The balance between apoptosis and proliferation in pulmonary artery smooth muscle cells (PASMCs) is important in maintaining normal pulmonary vascular structure. Activity of voltage-gated K(+) (K(V)) channels has been demonstrated to regulate cell apoptosis and proliferation. Treatment of PASMCs with staurosporine (ST) induced apoptosis in PASMCs, augmented K(V) current [I(K(V))], and induced mitochondrial Membrane Depolarization. High K(+) (40 mM) negligibly affected the ST-induced mitochondrial Membrane Depolarization but inhibited the ST-induced I(K(V)) increase and apoptosis. Blockade of K(V) channels with 4-aminopyridine diminished I(K(V)) and markedly decreased the ST-mediated apoptosis. Furthermore, the ST-induced apoptosis was preceded by the increase in I(K(V)). These results indicate that ST induces PASMC apoptosis by activation of plasmalemmal K(V) channels and mitochondrial Membrane Depolarization. The increased I(K(V)) would result in an apoptotic volume decrease due to a loss of cytosolic K(+) and induce apoptosis. The mitochondrial Membrane Depolarization would cause cytochrome c release, activate the cytosolic caspases, and induce apoptosis. Inhibition of K(V) channels would thus attenuate PASMC apoptosis.
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augmented k currents and mitochondrial Membrane Depolarization in pulmonary artery myocyte apoptosis
American Journal of Physiology-lung Cellular and Molecular Physiology, 2001Co-Authors: Stefanie Krick, Oleksandr Platoshyn, Sharon S. Mcdaniel, Lewis J. Rubin, Jason X.-j. YuanAbstract:The balance between apoptosis and proliferation in pulmonary artery smooth muscle cells (PASMCs) is important in maintaining normal pulmonary vascular structure. Activity of voltage-gated K(+) (K(V)) channels has been demonstrated to regulate cell apoptosis and proliferation. Treatment of PASMCs with staurosporine (ST) induced apoptosis in PASMCs, augmented K(V) current [I(K(V))], and induced mitochondrial Membrane Depolarization. High K(+) (40 mM) negligibly affected the ST-induced mitochondrial Membrane Depolarization but inhibited the ST-induced I(K(V)) increase and apoptosis. Blockade of K(V) channels with 4-aminopyridine diminished I(K(V)) and markedly decreased the ST-mediated apoptosis. Furthermore, the ST-induced apoptosis was preceded by the increase in I(K(V)). These results indicate that ST induces PASMC apoptosis by activation of plasmalemmal K(V) channels and mitochondrial Membrane Depolarization. The increased I(K(V)) would result in an apoptotic volume decrease due to a loss of cytosolic K(+) and induce apoptosis. The mitochondrial Membrane Depolarization would cause cytochrome c release, activate the cytosolic caspases, and induce apoptosis. Inhibition of K(V) channels would thus attenuate PASMC apoptosis.
Aron B. Fisher - One of the best experts on this subject based on the ideXlab platform.
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Membrane Depolarization is the trigger for pi3k akt activation and leads to the generation of ros
American Journal of Physiology-heart and Circulatory Physiology, 2012Co-Authors: Shampa Chatterjee, Elizabeth A. Browning, Nankang Hong, Kristine Debolt, Elena M. Sorokina, Weidong Liu, Morris J. Birnbaum, Aron B. FisherAbstract: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 KATP channel-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 KATP channel 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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Membrane Depolarization is the trigger for PI3K/Akt activation and leads to the generation of ROS
American journal of physiology. Heart and circulatory physiology, 2011Co-Authors: Shampa Chatterjee, Elizabeth A. Browning, Nankang Hong, Kristine Debolt, Elena M. Sorokina, Weidong Liu, Morris J. Birnbaum, Aron B. FisherAbstract: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 KATP channel-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 KATP channel 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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Membrane Depolarization and NADPH oxidase activation in aortic endothelium during ischemia reflect altered mechanotransduction.
American journal of physiology. Heart and circulatory physiology, 2004Co-Authors: Ikuo Matsuzaki, Shampa Chatterjee, Kris Debolt, Yefim Manevich, Qunwei Zhang, Aron B. FisherAbstract:We previously showed that “ischemia” (abrupt cessation of flow) leads to rapid Membrane Depolarization and increased generation of reactive oxygen species (ROS) in lung microvascular endothelial ce...
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ATP-independent Membrane Depolarization with Ischemia in the Oxygen-ventilated Isolated Rat Lung
American journal of respiratory cell and molecular biology, 1998Co-Authors: Abu B. Al-mehdi, Guochang Zhao, Aron B. FisherAbstract:We hypothesize that lung ischemic injury is related to cessation of flow leading to endothelial cell Membrane Depolarization and activation of oxidant-generating systems. Cell Membrane potential was assessed in isolated, oxygen ventilated, Krebs-Ringer bicarbonate buffer-dextran-perfused rat lungs by lung surface fluorescence after infusion of bis-oxonol or 5,5',6,6'-tetrachloro-1, 1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1), voltage-sensitive dyes. Surface fluorometry showed increased bis-oxonol fluorescence (34.7 +/- 3.3% above baseline) and decreased JC-1 fluorescence (24.5 +/- 4.5% below baseline) with ischemia, compatible with Membrane Depolarization. Fluorescence change was initiated within 1-2 min of the onset of ischemia and was rapidly reversible with reperfusion. Fluorescence changes varied with perfusion flow rate; maximal increase occurred with the transition from 1.8 ml/min to zero flow. Elevation of static intravascular pressure resulted in only a minor increase of bis-oxonol fluorescence. In situ subpleural fluorescence microscopy showed that endothelial cells are the major site of the increased bis-oxonol fluorescence signal with ischemia. These results indicate that endothelial cell Membrane Depolarization represents an early event with lung ischemia. Since the adenosine triphosphate content of lung was unchanged with ischemia in the O2-ventilated lungs, we postulate that Membrane Depolarization results from elimination of shear stress, possibly via inactivation of flow-sensitive K+-channels.
Yijen A. Huang - One of the best experts on this subject based on the ideXlab platform.
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Intracellular Ca2+ and TRPM5-mediated Membrane Depolarization produce ATP secretion from taste receptor cells
The Journal of Physiology, 2010Co-Authors: Yijen A. Huang, Stephen D. RoperAbstract:ATP is a transmitter secreted from taste bud receptor (Type II) cells through ATP-permeable gap junction hemichannels most probably composed of pannexin 1. The elevation of intracellular Ca2+ and Membrane Depolarization are both believed to be involved in transmitter secretion from receptor cells, but their specific roles have not been fully elucidated. In the present study, we show that taste-evoked ATP secretion from mouse vallate receptor cells is evoked by the combination of intracellular Ca2+ release and Membrane Depolarization. Unexpectedly, ATP secretion is not blocked by tetrodotoxin, indicating that transmitter release from these cells still takes place in the absence of action potentials. Taste-evoked ATP secretion is absent in receptor cells isolated from TRPM5 knockout mice or in taste cells from wild type mice where current through TRPM5 channels has been eliminated. These findings suggest that Membrane voltage initiated by TRPM5 channels is required for ATP secretion during taste reception. Nonetheless, even in the absence of TRPM5 channel activity, ATP release could be triggered by depolarizing cells with KCl. Collectively, the findings indicate that taste-evoked elevation of intracellular Ca2+ has a dual role: (1) Ca2+ opens TRPM5 channels to depolarize receptor cells and (2) Ca2+ plus Membrane Depolarization opens ATP-permeable gap junction hemichannels.
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Intracellular Ca(2+) and TRPM5-mediated Membrane Depolarization produce ATP secretion from taste receptor cells.
The Journal of physiology, 2010Co-Authors: Yijen A. Huang, Stephen D. RoperAbstract:ATP is a transmitter secreted from taste bud receptor (Type II) cells through ATP-permeable gap junction hemichannels most probably composed of pannexin 1. The elevation of intracellular Ca(2+) and Membrane Depolarization are both believed to be involved in transmitter secretion from receptor cells, but their specific roles have not been fully elucidated. In the present study, we show that taste-evoked ATP secretion from mouse vallate receptor cells is evoked by the combination of intracellular Ca(2+) release and Membrane Depolarization. Unexpectedly, ATP secretion is not blocked by tetrodotoxin, indicating that transmitter release from these cells still takes place in the absence of action potentials. Taste-evoked ATP secretion is absent in receptor cells isolated from TRPM5 knockout mice or in taste cells from wild type mice where current through TRPM5 channels has been eliminated. These findings suggest that Membrane voltage initiated by TRPM5 channels is required for ATP secretion during taste reception. Nonetheless, even in the absence of TRPM5 channel activity, ATP release could be triggered by depolarizing cells with KCl. Collectively, the findings indicate that taste-evoked elevation of intracellular Ca(2+) has a dual role: (1) Ca(2+) opens TRPM5 channels to depolarize receptor cells and (2) Ca(2+) plus Membrane Depolarization opens ATP-permeable gap junction hemichannels.