title: Differential Somatic Ca2+ Channel Profile in Midbrain Dopaminergic Neurons.
abstract: Dopaminergic (DA) neurons located in the ventral midbrain continuously generate a slow endogenous pacemaker activity, the mechanism of which is still debated. It has been suggested that, in the substantia nigra pars compacta (SNc), the pacemaking relies more on Ca(2+) channels and that the density of L-type Ca(2+) channels is higher in these DA neurons than in those located in the ventral tegmental area (VTA). This might lead to a higher Ca(2+) load in SNc DA neurons and explain their higher susceptibility to degeneration. However, direct evidence for this hypothesis is lacking. We found that the L-type current and channel density are indeed higher in the somata of rat SNc DA neurons and that this current undergoes less inactivation in this region. Nonstationary fluctuation analysis measurements showed a much higher number of L-type channels in the soma of SNc DA neurons, as well as a smaller single-channel conductance, pointing to a possible different molecular identity of L-type channels in DA neurons from the two areas. A major consequence of this is that pacemaking and, even more so, bursting are associated with a larger Ca(2+) entry through L-type channels in SNc DA neurons than in their VTA counterparts. Our results establish a molecular and functional difference between two populations of midbrain DA neurons that may contribute to their differential sensitivity to neurodegeneration.
  
  
  
  Dopamine neurons from the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) are involved in various brain functions, such as movement initiation and goal directed behavior, respectively. This work shows that, although both neurons fire in a similar regular and slow pacemaker mode, this firing activity is supported by different calcium channel landscapes. Indeed, the L-type calcium current is larger in the soma of dopamine neurons of the SNc, leading to a higher charge transfer through L-type channels during pacemaking and bursting. Therefore, these neurons may be physiologically exposed to a larger stress than their neighbors from the VTA.
authors.affiliation: Neurophysiology Unit, GIGA Neurosciences, University of Liège, B-4000 Liège, Belgium, and.
authors.forename: Fabian
authors.initials: F
authors.lastname: Philippart
authors.affiliation: Neurophysiology Unit, GIGA Neurosciences, University of Liège, B-4000 Liège, Belgium, and.
authors.forename: Geoffrey
authors.identifier: 0000-0001-9793-5643
authors.initials: G
authors.lastname: Destreel
authors.affiliation: Departamento de Anatomía Normal, Escuela de Medicina, and Centro Interdisciplinario de Neurociencias, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Paulina
authors.initials: P
authors.lastname: Merino-Sepúlveda
authors.affiliation: Departamento de Anatomía Normal, Escuela de Medicina, and Centro Interdisciplinario de Neurociencias, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Pablo
authors.identifier: 0000-0001-8470-8222
authors.initials: P
authors.lastname: Henny
authors.affiliation: Neurophysiology Unit, GIGA Neurosciences, University of Liège, B-4000 Liège, Belgium, and.
authors.forename: Dominique
authors.identifier: 0000-0002-5962-3152
authors.initials: D
authors.lastname: Engel
authors.affiliation: Neurophysiology Unit, GIGA Neurosciences, University of Liège, B-4000 Liège, Belgium, and V.Seutin@ulg.ac.be.
authors.forename: Vincent
authors.identifier: 0000-0002-8046-8142
authors.initials: V
authors.lastname: Seutin
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000145:classification / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000378:metabolism*; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008636:Mesencephalon / Q000166:cytology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014446:Tyrosine 3-Monooxygenase; D002118:Calcium
keywords: action potential clamp; dopaminergic neurons; neurodegeneration; nonstationary fluctuation analysis; nucleated patches; voltage-dependent calcium channels