{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:19:21Z","timestamp":1791299961050,"version":"4.1.0"},"reference-count":84,"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":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001543","name":"Neurological Foundation of New Zealand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001543","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":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Despite the importance of somatodendritic dopamine (DA) release in the Substantia Nigra<jats:italic>pars compacta<\/jats:italic>(SNc), its mechanism remains poorly understood. Using a novel approach combining fast\u2010scan controlled\u2010adsorption voltammetry (FSCAV) and single\u2010unit electrophysiology, we have investigated the mechanism of somatodendritic release by directly correlating basal (non\u2010stimulated) extracellular DA concentration ([DA]<jats:sub>out<\/jats:sub>), with pharmacologically\u2010induced changes of firing of nigral dopaminergic neurons in rat brain slices. FSCAV measurements indicated that basal [DA]<jats:sub>out<\/jats:sub>in the SNc was 40.7\u00a0\u00b1\u00a02.0\u00a0nM (at 34\u00a0\u00b1\u00a00.5\u00b0C), which was enhanced by amphetamine, cocaine, and L\u2010DOPA, and reduced by VMAT2 inhibitor, Ro4\u20101284. Complete inhibition of firing by TTX decreased basal [DA]<jats:sub>out<\/jats:sub>, but this reduction was smaller than the effect of D<jats:sub>2<\/jats:sub>receptor agonist, quinpirole. Despite similar effects on neuronal firing, the larger decrease in [DA]<jats:sub>out<\/jats:sub>evoked by quinpirole was attributed to cell membrane hyperpolarization and greater reduction in cytosolic free Ca<jats:sup>2+<\/jats:sup>([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>in<\/jats:sub>). Decreasing extracellular Ca<jats:sup>2+<\/jats:sup>also reduced basal [DA]<jats:sub>out<\/jats:sub>, despite increasing firing frequency. Furthermore, inhibiting L\u2010type Ca<jats:sup>2+<\/jats:sup>channels decreased basal [DA]<jats:sub>out<\/jats:sub>, although specific Ca<jats:sub>v<\/jats:sub>1.3 channel inhibition did not affect firing rate. Inhibition of sarcoplasmic\/endoplasmic reticulum Ca<jats:sup>2+<\/jats:sup>\u2010ATPase (SERCA) also decreased [DA]<jats:sub>out<\/jats:sub>, demonstrating the importance of intracellular Ca<jats:sup>2+<\/jats:sup>stores for somatodendritic release. Finally,<jats:italic>in\u00a0vivo<\/jats:italic>FSCAV measurements showed that basal [DA]<jats:sub>out<\/jats:sub>in the SNc was 79.8\u00a0\u00b1\u00a010.9\u00a0nM in urethane\u2010anesthetized rats, which was enhanced by amphetamine. Overall, our findings indicate that although tonic somatodendritic DA release is largely independent of action potentials, basal [DA]<jats:sub>out<\/jats:sub>is strongly regulated by voltage\u2010dependent Ca<jats:sup>2+<\/jats:sup>influx and release of intracellular Ca<jats:sup>2+<\/jats:sup>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Open science badges<\/jats:title><jats:p><jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/jnc14587-gra-0001.png\" xlink:title=\"image\"\/><\/jats:p><jats:p>This article has received a badge for<jats:bold>*Open Materials*<\/jats:bold>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<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/cos.io\/our-services\/open-science-badges\/\">https:\/\/cos.io\/our-services\/open-science-badges\/<\/jats:ext-link>.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14587-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14587","type":"journal-article","created":{"date-parts":[[2018,9,11]],"date-time":"2018-09-11T12:31:13Z","timestamp":1536669073000},"page":"462-479","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Action potential and calcium dependence of tonic somatodendritic dopamine release in the Substantia Nigra pars compacta"],"prefix":"10.1111","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0981-6634","authenticated-orcid":false,"given":"Andrew G.","family":"Yee","sequence":"first","affiliation":[{"name":"Department of Physiology and Centre for Brain Research University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blaze","family":"Forbes","sequence":"additional","affiliation":[{"name":"Department of Physiology and Centre for Brain Research University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pang\u2010Ying","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Physiology and Centre for Brain Research University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Martini","sequence":"additional","affiliation":[{"name":"Santa Lucia Foundation (IRCCS Fondazione Santa Lucia) Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark H.","family":"Burrell","sequence":"additional","affiliation":[{"name":"Department of Physiology and Centre for Brain Research University of Auckland Auckland New Zealand"},{"name":"Department of Physiology Development and Neuroscience University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Freestone","sequence":"additional","affiliation":[{"name":"Department of Physiology and Centre for Brain Research University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6109-8724","authenticated-orcid":false,"given":"Janusz","family":"Lipski","sequence":"additional","affiliation":[{"name":"Department of Physiology and Centre for Brain Research University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/la402686s"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4CC06165A"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.05.019"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)03047-0"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01904.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/S0022-3565(25)29539-8","article-title":"Dopaminergic neurons: effect of antipsychotic drugs and amphetamine on single cell activity","volume":"185","author":"Bunney B. 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