Mechanism of the medium‐duration afterhyperpolarization in rat serotonergic neurons. (4th November 2013)

• Record Type: Journal Article
• Authors: Alix, Philippe; Venkatesan, Kumar; Scuvée‐Moreau, Jacqueline; Massotte, Laurent; Nguyen Trung, Mai‐Linh; Cornil, Charlotte A.; Seutin, Vincent
• Is Part Of: European journal of neuroscience. Volume 39:Number 2(2014:Jan.)
• Page Start: 186
• Page End: 196
• Publication Date: 2013-11-04
• Subjects: Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.12408
• Languages: English
• ISSNs: 0953-816X

Abstract

<abstract abstract-type="main" id="ejn12408-abs-0001"> <title>Abstract</title> <p>Most serotonergic neurons display a prominent medium‐duration afterhyperpolarization (mAHP), which is mediated by small‐conductance Ca<sup>2+</sup>‐activated K<sup>+</sup> (SK) channels. Recent <italic>ex vivo</italic> and <italic>in vivo</italic> 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<sup>2+</sup> 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<sup>2+</sup> channel blocker Co<sup>2+</sup> and was partially blocked by both ω‐conotoxin and mibefradil, which are blockers of N‐type and T‐type Ca<sup>2+</sup> channels, respectively. Neither blockers of other voltage‐gated Ca<sup>2+</sup> channels nor DBHQ, an inhibitor of Ca<sup>2+</sup>‐induced Ca<sup>2+</sup> 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 <italic>in vivo</italic>‐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<sup>2+</sup> channels are the only source of Ca<sup>2+</sup> which activates the SK channels underlying the mAHP. T‐type Ca<sup>2+</sup> channels may also activate SK channels under different circumstances.</p> </abstract>