2,235 research outputs found

    Memorandum to Colonel W. L. Magill, Jr. Provost Marshal and Director of Evacuation

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    Memorandum to the Colonel W.L. Magill Jr., Provost Marshal and Director of Evacuation presumably from a committee with the following members: Galen M. Fisher, Gordon Chapman, C. A. Richardson, and F. H. Smith. The memo includes the following subtitles: General Purpose and General Considerations.The Bishop James Chamberlain Baker Collection includes letters, documents, and articles about Japanese Americans during World War II. Subjects in the collection include Japanese Americans mass removal, Pearl Harbor and the aftermath, religion, and support from the non-Japanese American community. The collection was digitized and made accessible online by CSUDH Gerth Archives and Special Collections

    Direct and specific activation of human inward rectifier K+ channels by membrane phosphatidylinositol 4,5-bisphosphate

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    Many ion channels are modulated by phosphatidylinositol 4,5-bisphosphate (PIP(2)), but studies examining the PIP(2) dependence of channel activity have been limited to cell expression systems, which present difficulties for controlling membrane composition. We have characterized the PIP(2) dependence of purified human Kir2.1 and Kir2.2 activity using (86)Rb(+) flux and patch clamp assays in liposomes of defined composition. We definitively show that these channels are directly activated by PIP(2) and that PIP(2) is absolutely required in the membrane for channel activity. The results provide the first quantitative description of the dependence of eukaryotic Kir channel function on PIP(2) levels in the membrane; Kir2.1 shows measureable activity in as little as 0.01% PIP(2), and open probability increases to ?0.4 at 1% PIP(2). Activation of Kir2.1 by phosphatidylinositol phosphates is also highly selective for PIP(2); PI, PI(4)P, and PI(5)P do not activate channels, and PI(3,4,5)P(3) causes minimal activity. The PIP(2) dependence of eukaryotic Kir activity is almost exactly opposite that of KirBac1.1, which shows marked inhibition by PIP(2). This raises the interesting hypothesis that PIP(2) activation of eukaryotic channels reflects an evolutionary adaptation of the channel to the appearance of PIP(2) in the eukaryotic cell membrane

    Dual-mode phospholipid regulation of human inward rectifying potassium channels

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    The lipid bilayer is a critical determinant of ion channel activity; however, efforts to define the lipid dependence of channel function have generally been limited to cellular expression systems in which the membrane composition cannot be fully controlled. We reconstituted purified human Kir2.1 and Kir2.2 channels into liposomes of defined composition to study their phospholipid dependence of activity using (86)Rb(+) flux and patch-clamp assays. Our results demonstrate that Kir2.1 and Kir2.2 have two distinct lipid requirements for activity: a specific requirement for phosphatidylinositol 4,5-bisphosphate (PIP(2)) and a nonspecific requirement for anionic phospholipids. Whereas we previously showed that PIP(2) increases the channel open probability, in this work we find that activation by POPG increases both the open probability and unitary conductance. Oleoyl CoA potently inhibits Kir2.1 by antagonizing the specific requirement for PIP(2), and EPC appears to antagonize activation by the nonspecific anionic requirement. Phosphatidylinositol phosphates can act on both lipid requirements, yielding variable and even opposite effects on Kir2.1 activity depending on the lipid background. Mutagenesis experiments point to the role of intracellular residues in activation by both PIP(2) and anionic phospholipids. In conclusion, we utilized purified proteins in defined lipid membranes to quantitatively determine the phospholipid requirements for human Kir channel activity
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