• apamin;
  • bicuculline methiodide;
  • SK channels;
  • voltage-dependent Ca2+ channels


Most serotonergic neurons display a prominent medium-duration afterhyperpolarization (mAHP), which is mediated by small-conductance 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 ω-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 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 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.