{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:59:50Z","timestamp":1790917190702,"version":"4.1.0"},"reference-count":42,"publisher":"American Physiological Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2012,6,1]]},"abstract":"<jats:p> Hypothalamic proopiomelanocortin (POMC) neurons are controlled by many central signals, including serotonin. Serotonin increases POMC activity and reduces feeding behavior via serotonion [5-hydroxytryptamine (5-HT)] receptors by modulating K<jats:sup>+<\/jats:sup> currents. A potential K<jats:sup>+<\/jats:sup> current is the M-current, a noninactivating, subthreshold outward K<jats:sup>+<\/jats:sup> current. Previously, we found that M-current activity was highly reduced in fasted vs. fed states in neuropeptide Y neurons. Because POMC neurons also respond to energy states, we hypothesized that fasting may alter the M-current and\/or its modulation by serotonergic input to POMC neurons. Using visualized-patch recording in neurons from fed male enhanced green fluorescent protein-POMC transgenic mice, we established that POMC neurons expressed a robust M-current (102.1 \u00b1 6.7 pA) that was antagonized by the selective KCNQ channel blocker XE-991 (40 \u03bcM). However, the XE-991-sensitive current in POMC neurons did not differ between fed and fasted states. To determine if serotonin suppresses the M-current via the 5-HT<jats:sub>2C<\/jats:sub> receptor, we examined the effects of the 5-HT<jats:sub>2A<\/jats:sub>\/5-HT<jats:sub>2C<\/jats:sub> receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) on the M-current. Indeed, DOI attenuated the M-current by 34.5 \u00b1 6.9% and 42.0 \u00b1 5.3% in POMC neurons from fed and fasted male mice, respectively. In addition, the 5-HT<jats:sub>1B<\/jats:sub>\/5-HT<jats:sub>2C<\/jats:sub> receptor agonist m-chlorophenylpiperazine attenuated the M-current by 42.4 \u00b1 5.4% in POMC neurons from fed male mice. Moreover, the selective 5-HT<jats:sub>2C<\/jats:sub> receptor antagonist RS-102221 abrogated the actions of DOI in suppressing the M-current. Collectively, these data suggest that although M-current expression does not differ between fed and fasted states in POMC neurons, serotonin inhibits the M-current via activation of 5-HT<jats:sub>2C<\/jats:sub> receptors to increase POMC neuronal excitability and, subsequently, reduce food intake. <\/jats:p>","DOI":"10.1152\/ajpendo.00565.2011","type":"journal-article","created":{"date-parts":[[2012,3,22]],"date-time":"2012-03-22T13:59:00Z","timestamp":1332424740000},"page":"E1399-E1406","source":"Crossref","is-referenced-by-count":44,"title":["Serotonin 5-HT<sub>2C<\/sub> receptor-mediated inhibition of the M-current in hypothalamic POMC neurons"],"prefix":"10.1152","volume":"302","author":[{"given":"T. A.","family":"Roepke","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. W.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O. K.","family":"R\u00f8nnekleiv","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon; and"},{"name":"Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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