Serotonin augments the cationic current Ih in central neurons.
Serotonin (5-HT) induced a slow depolarization when superfused onto neurons of the rat brainstem nucleus prepositus hypoglossi (PH) in vitro. The depolarization was associated with a decrease in cell input resistance. In voltage clamp, 5-HT caused an inward current that activated at approximately -50 mV and was present only at potentials negative to this. With hyperpolarizing voltage-clamp steps, PH neurons exhibited a slow inward current relaxation. The properties of this conductance were consistent with the cationic, nonselective current, Ih. Bath-applied 5-HT augmented Ih. Extracellular CsCl blocked both Ih and the inward current produced by 5-HT. In addition, forskolin, isobutylmethylxanthine, and 8-bromo-cAMP mimicked the inward current seen with 5-HT. The 5-HT1 agonist 5-carboxamidotryptamine produced a similar inward current. We conclude that 5-HT excites PH neurons by augmenting Ih, probably through receptor-mediated stimulation of adenylate cyclase. As Ih is found in many types of neurons, this mechanism may be a common mode of regulating cell excitability.
Bobker
D H
DH
Vollum Institute, Oregon Health Sciences University, Portland 97201.
Williams
J T
JT
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002412:Cations / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D007002:Hypoglossal Nerve; D015640:Ion Channel Gating / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*
D002412:Cations; D007473:Ion Channels; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012701:Serotonin; C047087:5-carboxamidotryptamine; D015056:1-Methyl-3-isobutylxanthine