title: Mechanism of the medium-duration afterhyperpolarization in rat serotonergic neurons.
abstract: Most serotonergic neurons display a prominent medium-duration afterhyperpolarization (mAHP), which is mediated by small-conductance Ca(2+) -activated K(+) (SK) channels. Recent ex vivo and in vivo experiments have suggested that SK channel blockade increases the firing rate and/or bursting in these neurons. The purpose of this study was therefore to characterize the source of Ca(2+) which activates the mAHP channels in serotonergic neurons. In voltage-clamp experiments, an outward current was recorded at -60 mV after a depolarizing pulse to +100 mV. A supramaximal concentration of the SK channel blockers apamin or (-)-bicuculline methiodide blocked this outward current. This current was also sensitive to the broad Ca(2+) channel blocker Co(2+) and was partially blocked by both ω-conotoxin and mibefradil, which are blockers of N-type and T-type Ca(2+) channels, respectively. Neither blockers of other voltage-gated Ca(2+) channels nor DBHQ, an inhibitor of Ca(2+)-induced Ca(2+) release, had any effect on the SK current. In current-clamp experiments, mAHPs following action potentials were only blocked by ω-conotoxin and were unaffected by mibefradil. This was observed in slices from both juvenile and adult rats. Finally, when these neurons were induced to fire in an in vivo-like pacemaker rate, only ω-conotoxin was able to increase their firing rate (by ~30%), an effect identical to the one previously reported for apamin. Our results demonstrate that N-type Ca(2+) channels are the only source of Ca(2+) which activates the SK channels underlying the mAHP. T-type Ca(2+) channels may also activate SK channels under different circumstances.
authors.affiliation: Neurophysiology Unit, GIGA Neurosciences, University of Liège, Liège, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Alix
authors.forename: Kumar
authors.initials: K
authors.lastname: Venkatesan
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Scuvée-Moreau
authors.forename: Laurent
authors.initials: L
authors.lastname: Massotte
authors.forename: Mai-Linh
authors.initials: ML
authors.lastname: Nguyen Trung
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Cornil
authors.forename: Vincent
authors.initials: V
authors.lastname: Seutin
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D059326:Serotonergic Neurons / Q000187:drug effects / Q000502:physiology*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020747:Calcium Channels, T-Type; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D002118:Calcium
keywords: SK channels; apamin; bicuculline methiodide; voltage-dependent Ca2+ channels