{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:14:23Z","timestamp":1791105263066,"version":"4.1.0"},"reference-count":62,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2005,3]]},"abstract":"<jats:p>Receptor-mediated dopamine (DA) modulation of neuronal excitability in the nucleus accumbens (NAc) has been shown to be critically involved in drug addiction and a variety of brain diseases. However, the mechanisms underlying the physiological or pathological molecular process of DA modulation remain largely elusive. Here, we demonstrate that stimulation of DA D<jats:sub>2<\/jats:sub>class receptors (D<jats:sub>2<\/jats:sub>R) enhanced voltage-sensitive sodium currents (VSSCs, I<jats:sub>Na<\/jats:sub>) in freshly dissociated NAc neurons via suppressing tonic activity of the cyclic AMP\/PKA cascade and facilitating intracellular Ca<jats:sup>2+<\/jats:sup>signaling. D<jats:sub>2<\/jats:sub>R-mediated I<jats:sub>Na<\/jats:sub>enhancement depended on activation of G<jats:sub>i\/o<\/jats:sub>proteins and was mimicked by direct inhibition of PKA. Furthermore, increasing free [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>in<\/jats:sub>by activating inositol 1,4,5-triphosphate receptors (IP<jats:sub>3<\/jats:sub>Rs), blocking Ca<jats:sup>2+<\/jats:sup>reuptake, or adding buffered Ca<jats:sup>2+<\/jats:sup>, all enhanced I<jats:sub>Na<\/jats:sub>. Under these circumstances, D<jats:sub>2<\/jats:sub>R-mediated I<jats:sub>Na<\/jats:sub>enhancement was occluded. In contrast, D<jats:sub>2<\/jats:sub>R-mediated I<jats:sub>Na<\/jats:sub>enhancement was blocked by inhibition of IP<jats:sub>3<\/jats:sub>Rs, chelation of free Ca<jats:sup>2+<\/jats:sup>, or inhibition of Ca<jats:sup>2+<\/jats:sup>\/calmodulin-activated calcineurin (CaN), but not by inhibition of phospholipase C (PLC). Although stimulation of muscarinic cholinergic receptors (mAChRs) also increased I<jats:sub>Na<\/jats:sub>, this action was blocked by PLC inhibitors. Our findings indicate that D<jats:sub>2<\/jats:sub>Rs mediate an enhancement of VSSCs in NAc neurons, in which cytosolic free Ca<jats:sup>2+<\/jats:sup>plays a crucial role. Our results also suggest that D<jats:sub>2<\/jats:sub>R-mediated reduction in tonic PKA activity may increase free [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>in<\/jats:sub>, primarily via disinhibition of IP<jats:sub>3<\/jats:sub>Rs. IP<jats:sub>3<\/jats:sub>R activation then facilitates Ca<jats:sup>2+<\/jats:sup>signaling and subsequently enhances VSSCs via decreasing PKA-induced phosphorylation and increasing CaN-induced dephosphorylation of Na<jats:sup>+<\/jats:sup>channels. This study provides insight into the complex and dynamic role of D<jats:sub>2<\/jats:sub>Rs in the NAc.<\/jats:p>","DOI":"10.1152\/jn.00771.2004","type":"journal-article","created":{"date-parts":[[2005,2,28]],"date-time":"2005-02-28T19:59:09Z","timestamp":1109620749000},"page":"1406-1417","source":"Crossref","is-referenced-by-count":31,"title":["Dopamine D<sub>2<\/sub>Receptor-Activated Ca<sup>2+<\/sup>Signaling Modulates Voltage-Sensitive Sodium Currents in Rat Nucleus Accumbens Neurons"],"prefix":"10.1152","volume":"93","author":[{"given":"Xiu-Ti","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu-Feng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis J.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-23-09650.1998"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/S1040-7952(98)80010-4"},{"key":"R3","unstructured":"Bers DM, Patton CW, and Nuccitelli R.A practical guide to the preparation of Ca2+buffers. In:A Practical Guide to the Study of Calcium in Living Cells\u2014The Methods in Cell Biology,edited by Nuccitelli R. New York: Academic, 1994, vol. 40, p. 3\u201329."},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1038\/351751a0"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.44.27582"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90124-8"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-19-07330.1997"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1016\/S1040-7952(97)80017-1"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1995.74.3.1343"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1007\/BF02801329"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.13.7750"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1038\/278265a0"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(94)90074-4"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.6.2232"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5378.838"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80384-0"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.10.5797"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1038\/361536a0"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013205230142"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80798-9"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(97)00057-X"},{"key":"R22","unstructured":"Gupta SKand Mishra RK.The effect of dopamine D1 and D2 receptor agonists on inositol phosphate turnover in rat striatal slices.Biochem Int22: 887\u2013894, 1990."},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1038\/23954"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-09-03334.1997"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-24-08987.2000"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00217.2004"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(92)90416-T"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1007\/BF00232868"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1988.tb01828.x"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90135-Z"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1126\/science.8396273"},{"key":"R32","doi-asserted-by":"crossref","unstructured":"Murphy BJ, Rossie S, De Jongh KS, and Catterall WA.Identification of the sites of selective phosphorylation and dephosphorylation of the rat brain Na+channel alpha subunit by cAMP-dependent protein kinase and phosphoprotein phosphatases.J Biol Chem268: 27355\u201327362, 1993.","DOI":"10.1016\/S0021-9258(19)74257-4"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1999.00724.x"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-21-08147.1997"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80282-2"},{"key":"R36","unstructured":"Parikh H, Liu L, Sibley DR and Chiodo LA.D2Sand D2Ldopamine receptors stably transfected in NG108-15 cells increase intracellular calcium via different signal transduction mechanisms.Neuroscience-Net1: 10007, 1996."},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.2385"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(94)90025-6"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(87)90724-2"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(88)90222-3"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.23.13900"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(92)90675-B"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(90)90616-S"},{"key":"R44","unstructured":"Sabala P, Czarny M, Woronczak JP, and Baranska J.Thapsigargin: potent inhibitor of Ca2+transport ATP-ases of endoplasmic and sarcoplasmic reticulum.Acta Biochim Pol40: 309\u2013319, 1993."},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1998.00142.x"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020570"},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00226-1"},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.36.040196.002333"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.22.8747"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90294-5"},{"key":"R51","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.21.10178"},{"key":"R52","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-02-00403.2003"},{"key":"R53","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0004(92)90009-X"},{"key":"R54","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.4.1613"},{"key":"R55","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01306-2"},{"key":"R56","doi-asserted-by":"crossref","unstructured":"White FJ, Hu X-T, and Zhang X-F.DA D2 receptors in the ventral striatum: multiple effects or receptor subtypes?Nihon Shinkei Seishin Yakurigaku Zasshi17: 91\u201395, 1997.","DOI":"10.1016\/0924-977X(96)87405-0"},{"key":"R57","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(92)90742-P"},{"key":"R58","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(97)01046-8"},{"key":"R59","doi-asserted-by":"crossref","unstructured":"Zamponi GWand French RJ.Sodium current inhibition by internal calcium: a combination of open-channel block and surface charge screening?J Membr Biol147: 1\u20136, 1995.","DOI":"10.1007\/BF00235393"},{"key":"R60","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.301.3.1119"},{"key":"R61","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-01-00488.1998"},{"key":"R62","unstructured":"Zhang X-Fand White FJ.Intracellular calcium regulates dopamine D2 receptor modulation of whole-cell sodium current in acutely dissociated nucleus accumbens neurons.Soc Neurosci Abstr23: 1280, 1997."}],"container-title":["Journal of Neurophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/jn.00771.2004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T04:44:00Z","timestamp":1625546640000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/jn.00771.2004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,3]]},"references-count":62,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2005,3]]}},"alternative-id":["10.1152\/jn.00771.2004"],"URL":"https:\/\/doi.org\/10.1152\/jn.00771.2004","relation":{},"ISSN":["0022-3077","1522-1598"],"issn-type":[{"value":"0022-3077","type":"print"},{"value":"1522-1598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,3]]}}}