{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:43:44Z","timestamp":1786977824305,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,3,24]],"date-time":"2011-03-24T00:00:00Z","timestamp":1300924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Microglia are critical cells in mediating the pathophysiology of neurodegenerative disorders such as HIV\u2010associated neurocognitive disorders. We hypothesize that HIV\u20101 glycoprotein 120 (gp120) activates microglia by enhancing outward K\n                    <jats:sup>+<\/jats:sup>\n                    currents, resulting in microglia secretion of neurotoxins, consequent neuronal dysfunction, and death. To test this hypothesis, we studied the effects of gp120 on outward K\n                    <jats:sup>+<\/jats:sup>\n                    current in cultured rat microglia. Application of gp120 enhanced outward K\n                    <jats:sup>+<\/jats:sup>\n                    current in a dose\u2010dependent manner, which was blocked by voltage\u2010gated K\n                    <jats:sup>+<\/jats:sup>\n                    (K\n                    <jats:sub>v<\/jats:sub>\n                    ) channel blockers. Western blot analysis revealed that gp120 produced an elevated expression of K\n                    <jats:sub>v<\/jats:sub>\n                    channel proteins. Examination of activation and inactivation of outward K\n                    <jats:sup>+<\/jats:sup>\n                    currents showed that gp120 shifted membrane potentials for activation and steady\u2010state inactivation. The gp120\u2010associated enhancement of outward K\n                    <jats:sup>+<\/jats:sup>\n                    current was blocked by either a CXCR4 receptor antagonist T140 or a specific protein kinase A (PKA) inhibitor H89, suggesting the involvement of chemokine receptor CXCR4 and PKA in gp120\u2010mediated enhancement of outward K\n                    <jats:sup>+<\/jats:sup>\n                    current. Biological significance of gp120\u2010induced enhancement of microglia outward K\n                    <jats:sup>+<\/jats:sup>\n                    current was demonstrated by experimental results showing the neurotoxic activity of gp120\u2010stimulated microglia, evaluated by TUNEL staining and MTT assay, significantly attenuated by K\n                    <jats:sub>v<\/jats:sub>\n                    channel blockers. Taken together, these results suggest that gp120 induces microglia neurotoxic activity by enhancing microglia outward K\n                    <jats:sup>+<\/jats:sup>\n                    current and that microglia K\n                    <jats:sub>v<\/jats:sub>\n                    channels may function as a potential target for the development of therapeutic strategies. \u00a9 2011 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/glia.21171","type":"journal-article","created":{"date-parts":[[2011,3,24]],"date-time":"2011-03-24T16:39:14Z","timestamp":1300984754000},"page":"997-1007","source":"Crossref","is-referenced-by-count":20,"title":["HIV\u20101 gp120 enhances outward potassium current via CXCR4 and cAMP\u2010dependent protein kinase a signaling in cultured rat microglia"],"prefix":"10.1002","volume":"59","author":[{"given":"Changshui","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianuo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangdong","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobutaka","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Tamamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huangui","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,3,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1995.268.2.H926"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.1.205-213.1999"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10826"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605136103"},{"key":"e_1_2_6_6_1","first-page":"1","volume-title":"Ligand 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