Utilizing current-clamp and single electrode voltage-clamp techniques we have studied the actions of serotonin (5-HT) on a transient outward voltage-dependent potassium current in adult rat Purkinje cells (PCs) in vitro. Under voltage-clamp, bath-applied 5-HT (10 nM-100 microM) reversibly depressed a transient outward potassium current in a dose-dependent manner in 24 of 26 neurons. This depression was apparent at all test command voltages. In current clamp, with normal bathing medium, 5-HT decreased the latency to first spike firing and increased the number of spikes in response to depolarization. Similar effects were evident when 4-aminopyridine was applied. In bathing medium containing TTX, Cs+ and Ni2+ to block voltage-activated currents, 5-HT increased the trajectory of the electrotonic membrane response elicited by depolarizing current injection. Enhanced responsiveness of PCs by 5-HT was not related to changes in membrane potential or input resistance. These experiments indicate that one mechanism by which 5-HT can increase the excitability of PCs is via reduction of a transient outward current.
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