{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:59:54Z","timestamp":1792216794861,"version":"4.4.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1998,10,6]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014Primary pulmonary hypertension (PPH) is a rare disease of unknown cause. Although PPH and secondary pulmonary hypertension (SPH) share many clinical and pathological characteristics, their origins may be disparate. In pulmonary artery smooth muscle cells (PASMCs), the activity of voltage-gated K\n            <jats:sup>+<\/jats:sup>\n            (K\n            <jats:sub>V<\/jats:sub>\n            ) channels governs membrane potential (E\n            <jats:sub>m<\/jats:sub>\n            ) and regulates cytosolic free Ca\n            <jats:sup>2+<\/jats:sup>\n            concentration ([Ca\n            <jats:sup>2+<\/jats:sup>\n            ]\n            <jats:sub>cyt<\/jats:sub>\n            ). A rise in [Ca\n            <jats:sup>2+<\/jats:sup>\n            ]\n            <jats:sub>cyt<\/jats:sub>\n            is a trigger of vasoconstriction and a stimulus of smooth muscle proliferation.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014Fluorescence microscopy and patch clamp techniques were used to measure [Ca\n            <jats:sup>2+<\/jats:sup>\n            ]\n            <jats:sub>cyt<\/jats:sub>\n            , E\n            <jats:sub>m<\/jats:sub>\n            , and K\n            <jats:sub>V<\/jats:sub>\n            currents in PASMCs. Mean pulmonary arterial pressures were comparable (46\u00b14 and 53\u00b14 mm Hg;\n            <jats:italic>P<\/jats:italic>\n            =0.30) in SPH and PPH patients. However, PPH-PASMCs had a higher resting [Ca\n            <jats:sup>2+<\/jats:sup>\n            ]\n            <jats:sub>cyt<\/jats:sub>\n            than cells from patients with SPH and nonpulmonary hypertension disease. Consistently, PPH-PASMCs had a more depolarized E\n            <jats:sub>m<\/jats:sub>\n            than SPH-PASMCs. Furthermore, K\n            <jats:sub>V<\/jats:sub>\n            currents were significantly diminished in PPH-PASMCs. Because of the dysfunctional K\n            <jats:sub>V<\/jats:sub>\n            channels, the response of [Ca\n            <jats:sup>2+<\/jats:sup>\n            ]\n            <jats:sub>cyt<\/jats:sub>\n            to the K\n            <jats:sub>V<\/jats:sub>\n            channel blocker 4-aminopyridine was significantly attenuated in PPH-PASMCs, whereas the response to 60 mmol\/L K\n            <jats:sup>+<\/jats:sup>\n            was comparable to that in SPH-PASMCs.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014These results indicate that K\n            <jats:sub>V<\/jats:sub>\n            channel function in PPH-PASMCs is inhibited compared with SPH-PASMCs. The resulting membrane depolarization and increase in [Ca\n            <jats:sup>2+<\/jats:sup>\n            ]\n            <jats:sub>cyt<\/jats:sub>\n            lead to pulmonary vasoconstriction and PASMC proliferation. Our data suggest that defects in PASMC K\n            <jats:sub>V<\/jats:sub>\n            channels in PPH patients may be a unique mechanism involved in initiating and maintaining pulmonary vasoconstriction and appear to play a role in the pathogenesis of PPH.\n          <\/jats:p>","DOI":"10.1161\/01.cir.98.14.1400","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:41:02Z","timestamp":1339461662000},"page":"1400-1406","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":369,"title":["Dysfunctional Voltage-Gated K\n            <sup>+<\/sup>\n            Channels in Pulmonary Artery Smooth Muscle Cells of Patients With Primary Pulmonary Hypertension"],"prefix":"10.1161","volume":"98","author":[{"given":"Jason Xiao-Jian","family":"Yuan","sequence":"first","affiliation":[{"name":"From the Departments of Medicine (J.X.-J.Y., A.M.A., J.W., S.P.G., J.B.O., L.J.R.), Physiology (J.X.-J.Y., M.J., L.J.R.), and Surgery (J.V.C.), University of Maryland School of Medicine, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann M.","family":"Aldinger","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (J.X.-J.Y., A.M.A., J.W., S.P.G., J.B.O., L.J.R.), Physiology (J.X.-J.Y., M.J., L.J.R.), and Surgery (J.V.C.), University of Maryland School of Medicine, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Juhaszova","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (J.X.-J.Y., A.M.A., J.W., S.P.G., J.B.O., L.J.R.), Physiology (J.X.-J.Y., M.J., L.J.R.), and Surgery (J.V.C.), University of Maryland School of Medicine, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (J.X.-J.Y., A.M.A., J.W., S.P.G., J.B.O., L.J.R.), Physiology (J.X.-J.Y., M.J., L.J.R.), and Surgery (J.V.C.), University of Maryland School of Medicine, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"John V.","family":"Conte","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (J.X.-J.Y., A.M.A., J.W., S.P.G., J.B.O., L.J.R.), Physiology (J.X.-J.Y., M.J., L.J.R.), and Surgery (J.V.C.), University of Maryland School of Medicine, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean P.","family":"Gaine","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (J.X.-J.Y., A.M.A., J.W., S.P.G., J.B.O., L.J.R.), Physiology (J.X.-J.Y., M.J., L.J.R.), and Surgery (J.V.C.), University of Maryland School of Medicine, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan B.","family":"Orens","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (J.X.-J.Y., A.M.A., J.W., S.P.G., J.B.O., L.J.R.), Physiology (J.X.-J.Y., M.J., L.J.R.), and Surgery (J.V.C.), University of Maryland School of Medicine, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis J.","family":"Rubin","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (J.X.-J.Y., A.M.A., J.W., S.P.G., J.B.O., L.J.R.), Physiology (J.X.-J.Y., M.J., L.J.R.), and Surgery (J.V.C.), University of Maryland School of Medicine, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199701093360207"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.80.5.2805259"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.72.2.8418981"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199105303242203"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199306173282402"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199507273330403"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199207093270202"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.20.4.557"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.42.6.1163"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.77.4.823"},{"key":"e_1_3_2_11_2","unstructured":"Pietra GG. 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