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.
de Vrind, V.; Scuvée-Moreau, Jacqueline; Drion, Guillaumeet al.
2016 • In European Journal of Pharmacology, 788, p. 274-279
Dopamine; SK Channels; Calcium; Pacemaker; Neurons
Abstract :
[en] Although small-conductance Ca2+-activated K+ (SK) channels and various types of voltage-gated Ca2+ (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 Ca2+ 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 Cd2+ 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 Ca2+ channels. Thus various sources of Ca2+ appear to be required for SK channel activation in SNc neurons (some of them still unidentified), ensuring robustness of pacemaking regularity.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
de Vrind, V.
Scuvée-Moreau, Jacqueline ; Université de Liège > Département des sciences biomédicales et précliniques > Pharmacologie
Drion, Guillaume ; Université de Liège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Systèmes et modélisation
Philippart, Fabian ; Université de Liège > Département des sciences biomédicales et précliniques > Pharmacologie
Engel, Dominique ; Université de Liège > Département des sciences biomédicales et précliniques > Pharmacologie
Seutin, Vincent ; Université de Liège > Département des sciences biomédicales et précliniques > Pharmacologie
Language :
English
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.
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