{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:09:50Z","timestamp":1791490190115,"version":"4.3.4"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"20","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,10,15]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Increased vascular Ca\n              <jats:sub>V<\/jats:sub>\n              1.2 channel function causes enhanced arterial tone during hypertension. This is mediated by elevations in angiotensin II\/protein kinase C signaling. Yet, the mechanisms underlying these changes are unclear. We hypothesize that \u03b11\n              <jats:sub>C<\/jats:sub>\n              phosphorylation at serine 1928 (S1928) is a key event mediating increased Ca\n              <jats:sub>V<\/jats:sub>\n              1.2 channel function and vascular reactivity during angiotensin II signaling and hypertension.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The hypothesis was examined in freshly isolated mesenteric arteries and arterial myocytes from control and angiotensin II\u2010infused mice. Specific techniques include superresolution imaging, proximity ligation assay, patch\u2010clamp electrophysiology, Ca\n              <jats:sup>2+<\/jats:sup>\n              imaging, pressure myography, laser speckle imaging, and blood pressure telemetry. Hierarchical \u201cnested\u201d and appropriate parametric or nonparametric\n              <jats:italic>t<\/jats:italic>\n              test and ANOVAs were used to assess statistical differences. We found that angiotensin II redistributed the Ca\n              <jats:sub>V<\/jats:sub>\n              1.2 pore\u2010forming \u03b11\n              <jats:sub>C<\/jats:sub>\n              subunit into larger clusters. This was correlated with elevated Ca\n              <jats:sub>V<\/jats:sub>\n              1.2 channel activity and cooperativity, global intracellular Ca\n              <jats:sup>2+<\/jats:sup>\n              and contraction of arterial myocytes, enhanced myogenic tone, and altered blood flow in wild\u2010type mice. These angiotensin II\u2010induced changes were prevented\/ameliorated in cells\/arteries from S1928 mutated to alanine knockin mice, which contain a negative modulation of the \u03b11\n              <jats:sub>C<\/jats:sub>\n              S1928 phosphorylation site. In angiotensin II\u2010induced hypertension, increased \u03b11\n              <jats:sub>C<\/jats:sub>\n              clustering, Ca\n              <jats:sub>V<\/jats:sub>\n              1.2 activity and cooperativity, myogenic tone, and blood pressure in wild\u2010type cells\/tissue\/mice were averted\/reduced in S1928 mutated to alanine samples.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Results suggest an essential role for \u03b11\n              <jats:sub>C<\/jats:sub>\n              S1928 phosphorylation in regulating channel distribution, activity and gating modality, and vascular function during angiotensin II signaling and hypertension. Phosphorylation of this single vascular \u03b11\n              <jats:sub>C<\/jats:sub>\n              amino acid could be a risk factor for hypertension that may be targeted for therapeutic intervention.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.035375","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T16:08:06Z","timestamp":1728403686000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["\u03b11\n            <sub>C<\/sub>\n            S1928 Phosphorylation of Ca\n            <sub>V<\/sub>\n            1.2 Channel Controls Vascular Reactivity and Blood Pressure"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8369-9192","authenticated-orcid":false,"given":"Victor A.","family":"Flores\u2010Tamez","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of California Davis Davis CA 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