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Mechanism of the medium‐duration afterhyperpolarization in rat serotonergic neurons
Author(s) -
Alix Philippe,
Venkatesan Kumar,
ScuvéeMoreau Jacqueline,
Massotte Laurent,
Nguyen Trung MaiLinh,
Cornil Charlotte A.,
Seutin Vincent
Publication year - 2014
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12408
Subject(s) - afterhyperpolarization , apamin , mibefradil , chemistry , serotonergic , bursting , neuroscience , patch clamp , channel blocker , electrophysiology , medicine , biophysics , endocrinology , voltage dependent calcium channel , potassium channel , serotonin , biology , calcium , receptor , biochemistry , organic chemistry
Most serotonergic neurons display a prominent medium‐duration afterhyperpolarization ( mAHP ), which is mediated by small‐conductance C a 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 C a 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 C a 2+ channel blocker C o 2+ and was partially blocked by both ω‐conotoxin and mibefradil, which are blockers of N ‐type and T ‐type C a 2+ channels, respectively. Neither blockers of other voltage‐gated C a 2+ channels nor DBHQ , an inhibitor of C a 2+ ‐induced C a 2+ release, had any effect on the SK current. In current‐clamp experiments, m AHP s 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 C a 2+ channels are the only source of C a 2+ which activates the SK channels underlying the m AHP . T‐type C a 2+ channels may also activate SK channels under different circumstances.