Serotonergic regulation of calcium-activated potassium currents in rodent prefrontal cortex.
In spite of a growing understanding of the actions of 5-hydroxytryptamine (5-HT) in the prefrontal cortex, the specific cellular mechanism used by 5-HT in this region remains poorly understood. Previous studies have shown that 5-HT inhibits the after hyper-polarization that follows a burst of spikes in pyramidal neurons. In the present study, we have used whole cell recordings in rat and mouse brain slices to re-examine this phenomenon with special emphasis on identifying the 5-HT receptor subtypes mediating this effect. Layer V pyramidal neurons display complex after hyper-polarizations that are mediated predominantly by calcium-activated potassium channels and involve two distinct currents known as medium after hyper-polarizating current and slow after hyper-polarizating current (I(sAHP)). Administration of 5-HT reduced the current underlying these after hyper-polarizations by selectively inhibiting I(sAHP). Pharmacological analysis of this response indicates that the main receptor responsible for this inhibition belongs to the 5-HT(2A) subtype. Thus, alpha-methyl-5-HT and 2,5-dimethoxy-4-bromoamphetamine (DOB) mimic the effect of 5-HT and the effect of these agonists is blocked by MDL 100 907. Similarly, administration of alpha-methyl-5-HT is without effect in slices derived from 5-HT(2A) receptor knockout mice. However, 5-HT(2A) receptor blockade only partially suppressed the ability of 5-HT to inhibit I(sAHP). This suggests the involvement of at least one more receptor subtype in this response. Consistent with this idea, administration of 5-carboxyamido-tryptamine, an agonist exhibiting no detectable affinity for 5-HT(2A) receptors, was also capable of suppressing I(sAHP). These results identify 5-HT(2A) receptors as being primarily involved in mediating the 5-HT-induced inhibition of I(sAHP) in prefrontal cortex, while also recognizing a contribution by an additional 5-HT receptor subtype.
Villalobos
Claudio
C
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Beique
Jean-Claude
JC
Gingrich
Jay A
JA
Andrade
Rodrigo
R
D000818:Animals; D000831:Animals, Newborn; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004347:Drug Interactions; D005464:Fluorobenzenes / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D017397:Prefrontal Cortex / Q000166:cytology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000172:deficiency; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D002121:Calcium Channel Blockers; D005464:Fluorobenzenes; D010880:Piperidines; D024681:Potassium Channels, Calcium-Activated; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D002104:Cadmium; D012701:Serotonin; C079049:volinanserin