Mechanism of the medium-duration afterhyperpolarization in rat serotonergic neurons.

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, m AHPs 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 m AHP. T-type Ca²⁺ channels may also activate SK channels under different circumstances. [ABSTRACT FROM AUTHOR]