{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:38Z","timestamp":1792787618717,"version":"4.5.0"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Heart, Lung, and Blood Institute","award":["R01 HL151190"],"award-info":[{"award-number":["R01 HL151190"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of Child Health and Human Development","award":["R01 HD090132"],"award-info":[{"award-number":["R01 HD090132"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    The hypothesized cellular and molecular mechanisms underlying dystonia are broad and include mutations that perturb Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling, including those affecting voltage gated calcium channels (VGCC). In mice, pharmacological activation of neuronal L-type VGCCs induces dystonia in a dose dependent manner. Here we demonstrate that mice expressing a gain-of-function mutation in the L-type VGCC Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2, associated with Timothy syndrome (TS), exhibit motor dysfunction consistent with dystonia. Although CaV1.2 is broadly expressed throughout peripheral tissues and across the brain, we establish that the dystonia-like behavior is driven by neuronal expression of the mutant calcium channel and observe an associated potential excitatory\/inhibitory (E\/I) imbalance. Because patients with TS have profound metabolic dysregulation, which is associated with some dystonias, we measured changes in circulating metabolites. The dystonia-like events are sensitive to perturbations in pyruvate metabolism, reminiscent of a subset of dystonias associated with pyruvate dysregulation. Our study provides insight into the potential convergence of previously established causes of dystonia, calcium signaling and metabolic homeostasis.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.207748","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:00:16Z","timestamp":1791302416000},"source":"Crossref","is-referenced-by-count":0,"title":["Dystonia in a Timothy syndrome mouse model uncovers an interaction between Ca2+ and metabolism"],"prefix":"10.1172","author":[{"given":"Patrick","family":"Towers","sequence":"first","affiliation":[{"name":"Cardiovascular Research Institute, Weill Cornell Medicine, New York, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Gang","family":"Wang","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Weill Cornell Medicine, New York, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9706-8244","authenticated-orcid":true,"given":"Maiko","family":"Matsui","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Weill Cornell Medicine, New York, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2246-0289","authenticated-orcid":true,"given":"Geoffrey S.","family":"Pitt","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Weill Cornell Medicine, New York, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,10,6]]},"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/insight.jci.org\/articles\/view\/207748\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:00:18Z","timestamp":1791302418000},"score":1,"resource":{"primary":{"URL":"http:\/\/insight.jci.org\/articles\/view\/207748"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":0,"alternative-id":["10.1172\/jci.insight.207748"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.207748","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]}}}