Action potential waveforms reveal simultaneous changes in I Ca and I K produced by 5-HT in rat dorsal raphe neurons

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Abstract
Action potentials were recorded from serotonergic dorsal raphe (DR) neurons acutely isolated from the adult rat brain. Action potential waveforms were used as command potentials for whole-cell patchclamp studies to investigate the Ca$^{2+}$ and K$^{+}$ currents underlying action potentials and the modulatory effects of 5-Hydroxytryptamine (5-HT) on them. These data were compared with currents elicited by using rectangular voltage steps of the type commonly used in voltage-clamp experiments. In the same cell, 5-HT simultaneously augmented K$^{+}$ currents and inhibited Ca$^{2+}$ currents. Experimental conditions were chosen which allowed us to examine the action of 5-HT on K$^{+}$ and Ca$^{2+}$ currents simultaneously or in isolation; 5-HT produced a larger inhibition of calcium current during an action potential waveform compared with that measured by using rectangular steps of voltage. A possible explanation for this finding is that the maximal inhibition is seen immediately after a voltage jump and then decreases with time. Action potentials are, in general, so brief that little time-dependent relief of block is observed. Most of the inhibition of Ca$^{2+}$ current resulted from a direct effect on Ca$^{2+}$ channels rather than a shortening of the action potential. The inhibition of Ca$^{2+}$ current by 5-HT also decreased the Ca$^{2+}$-activated K$^{+}$ currents. These results suggest that 5-HT reduces DR neuron excitability by the simultaneous activation of K$^{+}$ channel currents open at the resting potential and the suppression of Ca$^{2+}$ channel currents.