Excitatory effects of serotonin on rat striatal cholinergic interneurones.
We investigated the effects of 5-hydroxytryptamine (5-HT, serotonin) in striatal cholinergic interneurones with gramicidin-perforated whole-cell patch recordings. Bath-application of serotonin (30 microm) significantly and reversibly increased the spontaneous firing rate of 37/45 cholinergic interneurones tested. On average, in the presence of serotonin, firing rate was 273 +/- 193% of control. Selective agonists of 5-HT(1A), 5-HT3, 5-HT4 and 5-HT7 receptors did not affect cholinergic interneurone firing, while the 5-HT2 receptor agonist alpha-methyl-5-HT (30 microm) mimicked the excitatory effects of serotonin. Consistently, the 5-HT2 receptor antagonist ketanserin (10 microm) fully blocked the excitatory effects of serotonin. Two prominent after-hyperpolarizations (AHPs), one of medium duration that was apamin-sensitive and followed individual spikes, and one that was slower and followed trains of spikes, were both strongly and reversibly reduced by serotonin; these effects were fully blocked by ketanserin. Conversely, the depolarizing sags observed during negative current injections and mediated by hyperpolarization-activated cationic currents were not affected. In the presence of apamin and tetrodotoxin, the slow AHP was strongly reduced by 5-HT, and fully abolished by the calcium channel blocker nickel. These results show that 5-HT exerts a powerful excitatory control on cholinergic interneurones via 5-HT2 receptors, by suppressing the AHPs associated with two distinct calcium-activated potassium currents.
Blomeley
Craig
C
Faculty of Life Sciences, University of Manchester, Manchester M60 1QD, UK. e.bracci@manchester.ac.uk
Bracci
Enrico
E
D000109:Acetylcholine / Q000378:metabolism; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects* / Q000378:metabolism; D007650:Ketanserin / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D044348:Receptors, Serotonin, 5-HT2; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C042390:alpha-methylserotonin; D001030:Apamin; D012701:Serotonin; D009532:Nickel; D007650:Ketanserin; D000109:Acetylcholine