Serotonin alters an inwardly rectifying current (Ih) in rat cerebellar Purkinje cells under voltage clamp

The effects of serotonin (5-HT) on the hyperpolarization-activated sodium-potassium inward current (H-current: Ih) were examined in cerebellar Purkinje cells (PCs) under current- and voltage-clamp conditions. Quasi-steady state current versus voltage relationships under voltage clamp conditions showed that 5-HT decreased the inward rectification at potentials negative to -70 mV with a corresponding decrease in the slope conductance. In 70% of PCs, 5-HT produced dose-related attenuations of the Ih current with corresponding decreases in slope conductances across a range of hyperpolarized potentials. A negative shift in the Ih activation curve was elicited by 5-HT so that the amplitude of Ih current active near rest and at more hyperpolarized ranges was decreased. Serotonin-induced inhibition of Ih shows some receptor subtype selectivity in that DOI, the 5-HT2/IC receptor agonist, most closely mimicked the actions of 5-HT. This study reveals a novel inhibitory action of 5-HT on Ih in cerebellar Purkinje cells which may contribute to direct inhibitory effects of 5-HT on spontaneous firing and modulatory actions on gamma-aminobutyric acid (GABA)-mediated responses to PCs.