SEROTONIN ALTERS AN INWARDLY RECTIFYING CURRENT (I(H)) IN RAT CEREBELLAR PURKINJE-CELLS UNDER VOLTAGE-CLAMP

The effects of serotonin (5-HT) on the hyperpolarization-activated sodium-potassium inward current (H-current: I(h)) 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 I(h) current with corresponding decreases in slope conductances across a range of hyperpolarized potentials. A negative shift in the I(h) activation curve was elicited by 5-HT so that the amplitude of I(h) current active near rest and at more hyperpolarized ranges was decreased. Serotonin-induced inhibition of I(h) Shows some receptor subtype selectivity in that DOI, the 5-HT2/1C receptor agonist, most closely mimicked the actions of 5-HT. This study reveals a novel inhibitory action of 5-HT on I(h) 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 of PCs.