The action of 5-HT on calcium-dependent potassium channels and on the spinal locomotor network in lamprey is mediated by 5-HT1A-like receptors.
5-HT has a powerful modulatory action on the firing properties of single neurons as well as on locomotor activity. In lamprey, 5-HT increases the neuronal firing frequency in spinal neurons by reducing the conductance in Ca(2+)-dependent K+ channels (KCa) underlying the slow afterhyperpolarization (sAHP), and it also lowers the burst frequency of the spinal locomotor network. To elucidate which type of 5-HT receptor mediates these effects, different specific receptor agonists and antagonists were applied during intracellular current clamp recordings and during NMDA-induced fictive locomotion in the lamprey spinal cord in vitro preparation. The 5-HT1A receptor agonist 8-OH-DPAT ((+/-)-8-hydroxy-dipropylaminotetralin hydrobromide), the 5-HT1 receptor agonist 5-CT (5-carboxyamidotryptamine maleate) and the 5-HT2 receptor agonist alpha-CH3-5-HT (alpha-methylserotonin maleate) all reproduced the actions of 5-HT at both the cellular and the network levels. The effects of all agonists were completely or partially blocked by the 5-HT1A and 5-HT2 receptor antagonist spiperone (spiroperidol hydrochloride) while selective 5-HT2 receptor antagonists were ineffective. The selective 5-HT1A receptor antagonist S(-)-UH301 (S(-)-5-fluoro-8-hydroxy-dipropylaminotetralin hydrochloride) also counteracted the effect of 5-HT on the sAHP. 5-HT3 and 5-HT4 receptor agonists and antagonists were without effects. The intracellular coupling mechanism was not sensitive to pertussis toxin nor to the cAMP dependent protein kinase blocker (Rp)-cAMPS.(ABSTRACT TRUNCATED AT 250 WORDS)
Wikström
M
M
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Hill
R
R
Hellgren
J
J
Grillner
S
S
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D007798:Lampreys; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D015221:Potassium Channels; D011985:Receptors, Serotonin; D012701:Serotonin; D016202:N-Methylaspartate; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002118:Calcium