title: Interactions between calcium channels and SK channels in midbrain dopamine neurons and their impact on pacemaker regularity: Contrasting roles of N- and L-type channels.
abstract: Although small-conductance Ca(2+)-activated K(+) (SK) channels and various types of voltage-gated Ca(2+) (Cav) channels have been described in midbrain dopaminergic neurons, the nature of their interactions is unclear. More particularly, the role of various Cav channel types in either promoting irregularity of firing (by generating an inward current during SK channel blockade) or promoting regularity of firing (by providing the source of Ca(2+) for the activation of SK channels) has not been systematically explored. We addressed this question using intracellular and extracellular recordings from substantia nigra, pars compacta (SNc), dopaminergic neurons in rat midbrain slices. Neurons were pharmacologically isolated from their differences. When examining the ability of various Cav channel blockers to inhibit the SK-mediated afterhyperpolarization (AHP), we found that only the N-type Cav channel blocker ω-conotoxin-GVIA was able to reduce the apamin-sensitive AHP, but only partially (~40%). Specific blockers of L, P/Q, T or R channels had no effect on this AHP. Combining ω-conotoxin-GVIA and other specific blockers did not yield greater block and even the broad Cav blocker Cd(2+) induced a submaximal (~75%) effect. Extracellular recordings examining firing regularity yielded congruent results: none of the specific blockers was able to increase firing irregularity to the extent that the specific SK blocker apamin did. The irregularity of firing observed with apamin could only be reversed by blocking L-type Ca(2+) channels. Thus various sources of Ca(2+) appear to be required for SK channel activation in SNc neurons (some of them still unidentified), ensuring robustness of pacemaking regularity.
authors.affiliation: Laboratory of Neurophysiology, GIGA Neurosciences, University of Liège, Liège, Belgium; Brain Center Rudolph Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Veronne
authors.initials: V
authors.lastname: de Vrind
authors.affiliation: Laboratory of Neurophysiology, GIGA Neurosciences, University of Liège, Liège, Belgium.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Scuvée-Moreau
authors.affiliation: Department of Electrical Engineering and Computer Science, University of Liège, Liège, Belgium.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Drion
authors.affiliation: Laboratory of Neurophysiology, GIGA Neurosciences, University of Liège, Liège, Belgium.
authors.forename: Cyrine
authors.initials: C
authors.lastname: Hmaied
authors.affiliation: Laboratory of Neurophysiology, GIGA Neurosciences, University of Liège, Liège, Belgium.
authors.forename: Fabian
authors.initials: F
authors.lastname: Philippart
authors.affiliation: Laboratory of Neurophysiology, GIGA Neurosciences, University of Liège, Liège, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Engel
authors.affiliation: Laboratory of Neurophysiology, GIGA Neurosciences, University of Liège, Liège, Belgium. Electronic address: V.Seutin@ulg.ac.be.
authors.forename: Vincent
authors.initials: V
authors.lastname: Seutin
mesh_terms: D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001683:Biological Clocks / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008636:Mesencephalon / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin; D009543:Nifedipine
keywords: Ca(v) channels; Dopaminergic neurons; SK channel