Mechanism of the medium-duration afterhyperpolarization in rat serotonergic neurons

Alix, Philippe and Venkatesan, Kumar and Scuvée-Moreau, Jacqueline and Massotte, Laurent and Nguyen Trung, Mai-Linh and Cornil, Charlotte A. and Seutin, Vincent (2014) Mechanism of the medium-duration afterhyperpolarization in rat serotonergic neurons. European Journal of Neuroscience, 39 (2). pp. 186-196. ISSN 0953816X

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Most serotonergic neurons display a prominent medium-duration afterhyperpolarization (mAHP), which is mediated by smallconductance Ca2+-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 Ca2+ 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 Ca2+ channel blocker Co2+ and was partially blocked by both x-conotoxin and mibefradil, which are blockers of N-type and T-type Ca2+ channels, respectively. Neither blockers of other voltage-gated Ca2+ channels nor DBHQ, an inhibitor of Ca2+-induced Ca2+ release, had any effect on the SK current. In current-clamp experiments, mAHPs following action potentials were only blocked by x-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 x-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 Ca2+ channels are the only source of Ca2+ which activates the SK channels underlying the mAHP. T-type Ca2+ channels may also activate SK channels under different circumstances

Item Type: Article
Subjects: Pharmaceutical Sciences
Divisions: College of Pharmacy > Pharmaceutical Sciences
Depositing User: Dr KUMAR Venkatesan
Date Deposited: 15 May 2017 14:14
Last Modified: 15 May 2017 14:14

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