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The signal transduction pathways involved in these effects have not been characterized, but NT receptors are coupled to the phospholipase C pathway and Ca<jats:sup>2+<\/jats:sup>mobilization. However, an enhancement of intracellular Ca<jats:sup>2+<\/jats:sup>concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) evoked by NT in DAergic neurons has yet to be demonstrated. Furthermore, the hypothesis that the excitatory effects of NT in DAergic neurons are Ca<jats:sup>2+<\/jats:sup>dependant is currently untested. In whole-cell recording experiments, DAergic neurons in culture were identified by their selective ability to express a cell-specific green fluorescent protein reporter construct. These experiments confirmed that NT increases firing rate in cultured DAergic neurons. This effect was Ca<jats:sup>2+<\/jats:sup>dependent because it was blocked by intracellular dialysis with BAPTA. Using Ca<jats:sup>2+<\/jats:sup>imaging, we showed that NT caused a rapid increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>in DAergic neurons. Most of the Ca<jats:sup>2+<\/jats:sup>originated from the extracellular medium. NT-induced excitation and Ca<jats:sup>2+<\/jats:sup>influx were blocked by SR48692, an antagonist of the type 1 NT receptor. Blocking IP<jats:sub>3<\/jats:sub>receptors using heparin prevented the excitatory effect of NT. Moreover, Zn<jats:sup>2+<\/jats:sup>and<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"SKF96365\" ext-link-type=\"genpept\" xlink:type=\"simple\">SKF96365<\/jats:ext-link>both blocked the excitatory effect of NT, suggesting that nonselective cationic conductances are involved. Finally, although NT can also induce a rise in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>in astrocytes, we find that NT-evoked excitation of DAergic neurons can occur independently of astrocyte activation.<\/jats:p>","DOI":"10.1523\/jneurosci.5376-03.2004","type":"journal-article","created":{"date-parts":[[2004,3,10]],"date-time":"2004-03-10T22:52:59Z","timestamp":1078959179000},"page":"2566-2574","source":"Crossref","is-referenced-by-count":58,"title":["Role of Calcium in Neurotensin-Evoked Enhancement in Firing in Mesencephalic Dopamine 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