5-Hydroxytryptamine hyperpolarizes CA3 hippocampal pyramidal cells through an increase in potassium conductance.

The firing rate of hippocampal pyramidal cells recorded from the CA3 subfield is inhibited by 5-hydroxytryptamine (5-HT, serotonin) or by electrical stimulation of the ascending serotonergic fibers from the raphe. The mechanism of action of this inhibitory effect produced by 5-HT has not been determined. Intracellular recording techniques in the hippocampal slice preparation were used to measure the effect of 5-HT perfusion on membrane properties of CA3 pyramidal cells. In 15 out of 16 cells tested, 5-HT elicited a pronounced hyperpolarization concomitant with a decrease in membrane resistance. The hyperpolarization was not altered with either potassium chloride or potassium methylsulphate electrodes; the hyperpolarization by 5-HT was not present when electrodes were filled with cesium chloride. The reversal potential of the 5-HT mediated response was determined to be-105.5 mV in 3 mM KCl buffer using single electrode voltage clamp techniques. Based on these results we conclude that the mechanism of action of the 5-HT inhibition of CA3 hippocampal pyramidal cell excitability is due to an increase in potassium conductance.