Evidence for a modulatory role of Ih on the firing of a subgroup of midbrain dopamine neurons.
A previous investigation has suggested that the hyperpolarization-activated cation current Ih does not contribute to the spontaneous firing of midbrain dopaminergic neurons. This conclusion was reached using Cs(-1). We have re-examined this question with extracellular recordings in slices using the more specific blocker ZD7288. In two-thirds of the cells, low concentrations of ZD7288 induced a decrease of the spontaneous firing. The maximal inhibition was about 40% and the mean IC50 was 1.6 microM. This effect was probably direct because it persisted in the presence of antagonists of various receptors. These concentrations of ZD7288 had no effect in the remaining one third of the examined cells. However, the highest concentration of ZD7288 (300 microM) abolished the firing of all dopaminergic neurons, probably by a mechanism unrelated to the blockade of Ih. We conclude that Ih controls to a certain extent the firing of a majority of midbrain dopaminergic neurons.
Seutin
V
V
Research Center for Cellular and Molecular Neurobiology, University of Liège, Tour de Pathologie, Sart Tilman/Liège I, Belgium.
Massotte
L
L
Renette
M F
MF
Dresse
A
A
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D002317:Cardiovascular Agents / Q000494:pharmacology; D002412:Cations / Q000378:metabolism; D002586:Cesium / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D008636:Mesencephalon / Q000166:cytology* / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013469:Sulpiride / Q000494:pharmacology
D015220:Calcium Channels; D002317:Cardiovascular Agents; D002412:Cations; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D011743:Pyrimidines; C082246:ICI D2788; D002586:Cesium; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D013469:Sulpiride; C066430:CGP 35348; D002118:Calcium; D004298:Dopamine