5-HT inhibits N-type but not L-type Ca(2+) channels via 5-HT1A receptors in lamprey spinal neurons.
5-HT is a potent modulator of locomotor activity in vertebrates. In the lamprey, 5-HT dramatically slows fictive swimming. At the neuronal level it reduces the postspike slow afterhyperpolarization (sAHP), which is due to apamin-sensitive Ca(2+)-dependent K+ channels (KCa). Indirect evidence in early experiments suggested that the sAHP reduction results from a direct action of 5-HT on KCa channels rather than an effect on the Ca(2+) entry during the action potential. In view of the characterization of different subtypes of Ca(2+) channels with very different properties, we now reinvestigate if there is a selective action of 5-HT on a Ca(2+) channel subtype in dissociated spinal neurons in culture. 5-HT reduced Ca(2+) currents from high voltage activated channels. N-type, but not L-type, Ca(2+) channel blockers abolished this 5-HT-induced reduction. It was also confirmed that 5-HT depresses Ca(2+) currents in neurons, including motoneurons, in the intact spinal cord. 8-OH-DPAT, a 5-HT1A receptor agonist, also inhibited Ca(2+) currents in dissociated neurons. After incubation in pertussis toxin, to block Gi/o proteins, 5-HT did not reduce Ca(2+) currents, further indicating that the effect is caused by an activation of 5-HT1A receptors. As N-type, but not L-type, Ca(2+) channels are known to mediate the activation of KCa channels and presynaptic transmitter release at lamprey synapses, the effects of 5-HT reported here can contribute to a reduction in both actions.
Hill
Russell H
RH
Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm, Sweden. Russell.Hill@neuro.ki.se
Svensson
Erik
E
Dewael
Yannick
Y
Grillner
Sten
S
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004347:Drug Interactions; D004553:Electric Conductivity; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D007798:Lampreys; D007814:Larva; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D037342:Pertussis Toxin / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology* / Q000502:physiology; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D016166:Free Radical Scavengers; D026902:Potassium Channel Blockers; D017366:Serotonin Receptor Agonists; D002104:Cadmium; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006160:Guanosine Triphosphate; C040518:gamma-(4-aminophenyl) 7-methylguanosine 5'-triphosphate; D020866:omega-Conotoxin GVIA; D037342:Pertussis Toxin; D002118:Calcium