Reference : SK channels control the firing pattern of midbrain dopaminergic neurons in vivo
Scientific journals : Article
Social & behavioral sciences, psychology : Neurosciences & behavior
http://hdl.handle.net/2268/5137
SK channels control the firing pattern of midbrain dopaminergic neurons in vivo
English
Waroux, Olivier [Université de Liège - ULg > > Pharmacologie >]
Massotte, Laurent mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques >]
Alleva, Livia mailto [Université de Liège - ULg > Département des sciences cognitives > Neuroscience comportementale et psychopharmacologie expér. >]
Graulich, Amaury [Université de Liège - ULg > > Chimie pharmaceutique >]
Thomas, E. [> > > >]
Liégeois, Jean-François mailto [Université de Liège - ULg > Département de pharmacie > Chimie pharmaceutique >]
Scuvée-Moreau, Jacqueline mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Pharmacologie - Département des sciences biomédicales et précliniques >]
Seutin, Vincent mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Pharmacologie >]
Dec-2005
European Journal of Neuroscience
Blackwell Publishing
22
12
3111-3121
Yes (verified by ORBi)
International
0953-816X
Oxford
[en] burst firing ; extracellular recordings ; iontophoresis ; Parkinson's disease ; rat
[en] A vast body of experimental in vitro work and modelling studies suggests that the firing pattern and/or rate of a majority of midbrain dopaminergic neurons may be controlled in part by Ca2+-activated K+ channels of the SK type. However, due to the lack of suitable tools, in vivo evidence is lacking. We have taken advantage of the development of the water-soluble, medium potency SK blocker N-methyl-laudanosine (CH3-L) to test this hypothesis in anaesthetized rats. In the lateral ventral tegmental area, CH3-L iontophoresis onto dopaminergic neurons significantly increased the coefficient of variation of their interspike intervals and the percentage of spikes generated in bursts as compared to the control condition. The effect of CH3-L persisted in the presence of a specific GABA(A) antagonist, suggesting a direct effect. It was robust and reversible, and was also observed in the substantia nigra. Control experiments demonstrated that the effect of CH3-L could be entirely ascribed to its blockade of SK channels. On the other hand, the firing pattern of noradrenergic neurons was much less affected by CH3-L. We provide here the first demonstration of a major role of SK channels in the control of the switch between tonic and burst firing of dopaminergic neurons in physiological conditions. This study also suggests a new strategy to develop modulators of the dopaminergic (DA) system, which could be of interest in the treatment of Parkinson's disease, and perhaps other diseases in which DA pathways are dysfunctional.
http://hdl.handle.net/2268/5137
10.1111/j.1460-9568.2005.04484.x

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