Serotonergic regulation of calcium-activated potassium currents in rodent prefrontal cortex

Eur J Neurosci. 2005 Sep;22(5):1120-6. doi: 10.1111/j.1460-9568.2005.04307.x.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cadmium / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Drug Interactions
  • Fluorobenzenes / pharmacology
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / drug effects
  • Neurons / physiology*
  • Piperidines / pharmacology
  • Potassium Channels, Calcium-Activated / physiology*
  • Prefrontal Cortex / cytology*
  • Prefrontal Cortex / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2A / deficiency
  • Serotonin / physiology*
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology


  • Calcium Channel Blockers
  • Fluorobenzenes
  • Piperidines
  • Potassium Channels, Calcium-Activated
  • Receptor, Serotonin, 5-HT2A
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Cadmium
  • Serotonin
  • volinanserin