Changes in membrane potential of frog motoneurons induced by activation of serotonin receptor subtypes.
Application of serotonin to the isolated, hemisected frog spinal cord resulted in two distinctive changes in motoneuron membrane potential: hyperpolarizations were produced by low concentrations (0.01-1.0 microM) and depolarizations by higher concentrations (3.0-100 microM). The hyperpolarizations appeared to be caused by a direct action of the amine upon motoneurons since exposure of spinal cord tetrodotoxin or magnesium ions in concentrations which blocked interneuronal firing and synaptic transmission, respectively did not reduce these responses. In contrast, depolarizations were significantly reduced by tetrodotoxin or magnesium indicating a large indirect component. The use of agonists and antagonists known to discriminate among different subtypes of serotonin receptors indicated that the hyperpolarizations were produced by activation of 5-HT1A receptors and the depolarizations were generated by activation of 5-HT2 and/or 5-HT1C receptors. Accordingly, the selective 5-HT1A agonists 8-hydroxy-2-(n-dipropylamino)tetralin and ipsapirone directly hyperpolarized motoneurons. The changes in potential produced by low concentrations of serotonin and by these agonists were blocked by the 5-HT1A receptor antagonists spiperone and spiroxatrine. In contrast, application of high concentrations of alpha-methyl-5-hydroxytryptamine, a serotonin analog which activates 5-HT1C and 5-HT2 receptor subtypes, depolarized motoneurons. These depolarizations, and those produced by high concentrations of serotonin, were blocked by the 5-HT1C/5-HT2 antagonists ketanserin, methysergide and mianserin. These observations indicate that serotonin can alter the membrane potential of motoneurons directly and indirectly by activation of both 5-HT1 and 5-HT2 receptor subtypes. Activation of different receptor subtypes depends upon the concentration of the amine.
Holohean
A M
AM
Department of Neurology, University of Miami School of Medicine, FL 33101.
Hackman
J C
JC
Davidoff
R A
RA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D008564:Membrane Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D011743:Pyrimidines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013134:Spiperone / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D011743:Pyrimidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D013134:Spiperone; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin