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Here, we tested the hypothesis that <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>4<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content> activation regulates the activity of voltage\u2010gated calcium channels and, as a consequence, synaptic activity. We also tested whether the proposed effect occurs in the amygdala, a brain area known to mediate the anorexigenic actions of <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>4<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content> signaling. Using the patch\u2010clamp technique, we found that the activation of <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>4<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content> with its agonist melanotan <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> specifically inhibited 34.5\u00a0\u00b1\u00a01.5% of N\u2010type calcium currents in transiently transfected <jats:styled-content style=\"fixed-case\">HEK<\/jats:styled-content>293 cells. This inhibition was concentration\u2010dependent, voltage\u2010independent and occluded by the G\u03b1<jats:sub>s<\/jats:sub> pathway inhibitor cholera toxin. Moreover, we found that melanotan <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> specifically inhibited 25.9\u00a0\u00b1\u00a02.0% of native N\u2010type calcium currents and 55.4\u00a0\u00b1\u00a014.4% of evoked inhibitory postsynaptic currents in mouse cultured amygdala neurons. <jats:italic>In\u00a0vivo<\/jats:italic>, we found that the <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>4R agonist <jats:styled-content style=\"fixed-case\">RO<\/jats:styled-content>27\u20103225 increased the marker of cellular activity c\u2010Fos in several components of the amygdala, whereas the N\u2010type channel blocker \u03c9 conotoxin <jats:styled-content style=\"fixed-case\">GVIA<\/jats:styled-content> increased c\u2010Fos expression exclusively in the central subdivision of the amygdala. Thus, <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>4R specifically inhibited the presynaptic N\u2010type channel subtype, and this inhibition may be important for the effects of melanocortin in the central subdivision of the amygdala.<\/jats:p>","DOI":"10.1111\/ejn.12650","type":"journal-article","created":{"date-parts":[[2014,6,18]],"date-time":"2014-06-18T16:40:20Z","timestamp":1403109620000},"page":"2755-2765","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Melanocortin 4 receptor activation inhibits presynaptic N\u2010type calcium channels in amygdaloid complex neurons"],"prefix":"10.1111","volume":"40","author":[{"given":"Francina","family":"Agosti","sequence":"first","affiliation":[{"name":"Laboratory of Electrophysiology Multidisciplinary Institute of Cell Biology (IMBICE) Argentine Research Council (CONICET) and Scientific Research Commission Province of Buenos Aires (CIC\u2010PBA) La 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