{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T16:56:11Z","timestamp":1773420971816,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T00:00:00Z","timestamp":1541980800000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","award":["766124"],"award-info":[{"award-number":["766124"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["2016\u201078892\u2010R"],"award-info":[{"award-number":["2016\u201078892\u2010R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2018,11]]},"abstract":"Abstract<\/jats:title>As the peripheral sympathoadrenal axis is tightly controlled by the cortex via hypothalamus and brain stem, the central pathological features of Hunting's disease, (HD<\/jats:styled-content>) that is, deposition of mutated huntingtin and synaptic dysfunctions, could also be expressed in adrenal chromaffin cells. To test this hypothesis we here present a thorough investigation on the pathological and functional changes undergone by chromaffin cells (CC<\/jats:styled-content>s) from 2\u2010month (2\u00a0m) to 7\u2010month (7\u00a0m) aged wild\u2010type (WT<\/jats:styled-content>) and R6\/1 mouse model of Huntington's disease (HD<\/jats:styled-content>), stimulated with acetylcholine (AC<\/jats:styled-content>h) or high [K+<\/jats:sup>] (K+<\/jats:sup>). In order to do this, we used different techniques such as inmunohistochemistry, patch\u2010clamp, and amperometric recording. With respect to WT<\/jats:styled-content> cells, some of the changes next summarized were already observed in HD<\/jats:styled-content> mice at a pre\u2010disease stage (2\u00a0m); however, they were more pronounced at 7\u00a0m when motor deficits were clearly established, as follows: (i) huntingtin over\u2010expression as nuclear aggregates in CC<\/jats:styled-content>s; (ii) smaller CC<\/jats:styled-content> size with decreased dopamine \u03b2\u2010hydroxylase expression, indicating lesser number of chromaffin secretory vesicles; (iii) reduced adrenal tissue catecholamine content; (iv) reduced Na+<\/jats:sup> currents with (v) membrane hyperpolarization and reduced AC<\/jats:styled-content>h\u2010evoked action potentials; (v) reduced [Ca2+<\/jats:sup>]c<\/jats:sub> transients with faster Ca2+<\/jats:sup> clearance; (vi) diminished quantal secretion with smaller vesicle quantal size; (vii) faster kinetics of the exocytotic fusion pore, pore expansion, and closure. On the basis of these data, the hypothesis is here raised in the sense that nuclear deposition of mutated huntingtin in adrenal CC<\/jats:styled-content>s of R6\/1 mice could be primarily responsible for poorer Na+<\/jats:sup> channel expression and function, giving rise to profound depression of cell excitability, altered Ca2+<\/jats:sup> handling and exocytosis.<\/jats:p><\/jats:sec>Open Practices<\/jats:title><\/jats:p>This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https:\/\/cos.io\/our-services\/open-science-badges\/<\/jats:ext-link>.<\/jats:p><\/jats:sec>\nimage<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p>Cover Image for this issue: doi: 10.1111\/jnc.14201<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14585","type":"journal-article","created":{"date-parts":[[2018,9,5]],"date-time":"2018-09-05T07:07:24Z","timestamp":1536131244000},"page":"454-476","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Altered excitability and exocytosis in chromaffin cells from the R6\/1 mouse model of Huntington's disease is linked to over\u2010expression of mutated huntingtin"],"prefix":"10.1111","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0593-792X","authenticated-orcid":false,"given":"Carmen","family":"Mart\u00ednez\u2010Ram\u00edrez","sequence":"first","affiliation":[{"name":"Instituto Te\u00f3filo Hernando C\/Faraday Madrid Spain"},{"name":"Departamento de Farmacolog\u00eda y Terap\u00e9utica Universidad Aut\u00f3noma de Madrid Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital Universitario de La Princesa Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9s M.","family":"Baraibar","sequence":"additional","affiliation":[{"name":"Instituto Te\u00f3filo Hernando C\/Faraday Madrid Spain"},{"name":"Departamento de Farmacolog\u00eda y Terap\u00e9utica Universidad Aut\u00f3noma de Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Nanclares","sequence":"additional","affiliation":[{"name":"Instituto Te\u00f3filo Hernando C\/Faraday Madrid Spain"},{"name":"Departamento de Farmacolog\u00eda y Terap\u00e9utica Universidad Aut\u00f3noma de Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iago","family":"M\u00e9ndez\u2010L\u00f3pez","sequence":"additional","affiliation":[{"name":"Instituto Te\u00f3filo Hernando C\/Faraday Madrid Spain"},{"name":"Departamento de Farmacolog\u00eda y Terap\u00e9utica Universidad Aut\u00f3noma de Madrid Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital Universitario de La Princesa Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital Universitario Ram\u00f3n y Cajal Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u1d43 Paz","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital Universitario Ram\u00f3n y Cajal Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio M. 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