M-type channels selectively control bursting in rat  dopaminergic neurons.
Midbrain dopaminergic neurons in the substantia nigra, pars compacta and ventral tegmental area are critically important in many physiological functions. These neurons exhibit firing patterns that include tonic slow pacemaking, irregular firing and bursting, and the amount of dopamine that is present in the synaptic cleft is much increased during bursting. The mechanisms responsible for the switch between these spiking patterns remain unclear. Using both in-vivo recordings combined with microiontophoretic or intraperitoneal drug applications and in-vitro experiments, we have found that M-type channels, which are present in midbrain dopaminergic cells, modulate the firing during bursting without affecting the background low-frequency pacemaker firing. Thus, a selective blocker of these channels, 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride, specifically potentiated burst firing. Computer modeling of the dopamine neuron confirmed the possibility of a differential influence of M-type channels on excitability during various firing patterns. Therefore, these channels may provide a novel target for the treatment of dopamine-related diseases, including Parkinson's disease and drug addiction. Moreover, our results demonstrate that the influence of M-type channels on the excitability of these slow pacemaker neurons is conditional upon their firing pattern.
Drion
Guillaume
G
Laboratory of Pharmacology and GIGA Neurosciences, University of Liège, Belgium.
Bonjean
Maxime
M
Waroux
Olivier
O
Scuvée-Moreau
Jacqueline
J
Liégeois
Jean-Françis
JF
Sejnowski
Terrence J
TJ
Sepulchre
Rodolphe
R
Seutin
Vincent
V
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D003198:Computer Simulation; D004298:Dopamine / Q000378:metabolism; D051656:KCNQ Potassium Channels / Q000378:metabolism*; D008297:Male; D008636:Mesencephalon / Q000378:metabolism; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar
D051656:KCNQ Potassium Channels; C492166:Kcnq4 protein, rat; D004298:Dopamine