title: Somatodendritic dopamine release requires synaptotagmin 4 and 7 and the participation of voltage-gated calcium channels.
abstract: Somatodendritic (STD) dopamine (DA) release is a key mechanism for the autoregulatory control of DA release in the brain. However, its molecular mechanism remains undetermined. We tested the hypothesis that differential expression of synaptotagmin (Syt) isoforms explains some of the differential properties of terminal and STD DA release. Down-regulation of the dendritically expressed Syt4 and Syt7 severely reduced STD DA release, whereas terminal release required Syt1. Moreover, we found that although mobilization of intracellular Ca(2+) stores is inefficient, Ca(2+) influx through N- and P/Q-type voltage-gated channels is critical to trigger STD DA release. Our findings provide an explanation for the differential Ca(2+) requirement of terminal and STD DA release. In addition, we propose that not all sources of intracellular Ca(2+) are equally efficient to trigger this release mechanism. Our findings have implications for a better understanding of a fundamental cell biological process mediating transcellular signaling in a system critical for diseases such as Parkinson disease.
authors.affiliation: Department of Pharmacology, Groupe de Recherche sur le Système Nerveux Central, Faculty of Medicine, Université de Montréal, Montréal, Québec H3C 3J7, Canada.
authors.forename: Jose Alfredo
authors.initials: JA
authors.lastname: Mendez
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Bourque
authors.forename: Caroline
authors.initials: C
authors.lastname: Fasano
authors.forename: Christian
authors.initials: C
authors.lastname: Kortleven
authors.forename: Louis-Eric
authors.initials: LE
authors.lastname: Trudeau
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism; D050857:Synaptotagmins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D009419:Nerve Tissue Proteins; C494293:Syt4 protein, mouse; C494303:Syt7 protein, mouse; D050857:Synaptotagmins; D002118:Calcium; D004298:Dopamine