5-HT inhibits N-type but not L-type Ca(2+) channels via 5-HT1A receptors in lamprey spinal neurons

• Published in: The European journal of neuroscience Vol. 18; no. 11; p. 2919
• Main Authors: Hill, Russell H, Svensson, Erik, Dewael, Yannick, Grillner, Sten
• Format: Journal Article
• Language: English
• Published: France 01.12.2003
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; Anesthetics, Local - pharmacology; Animals; Cadmium - pharmacology; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channels, L-Type - metabolism; Calcium Channels, N-Type - drug effects; Calcium Channels, N-Type - metabolism; Cells, Cultured; Drug Interactions; Electric Conductivity; Free Radical Scavengers - pharmacology; Guanosine Triphosphate - analogs & derivatives; Guanosine Triphosphate - pharmacology; Lampreys; Larva; Medicin och hälsovetenskap; Membrane Potentials - drug effects; Neurons - drug effects; Neurons - metabolism; omega-Conotoxin GVIA - pharmacology; Patch-Clamp Techniques - methods; Pertussis Toxin - pharmacology; Potassium Channel Blockers - pharmacology; Receptor, Serotonin, 5-HT1A - physiology; Serotonin - pharmacology; Serotonin Receptor Agonists - pharmacology; Spinal Cord - cytology; Spinal Cord - physiology; Tetraethylammonium - pharmacology; Tetrodotoxin - pharmacology; Time Factors
• ISSN: 0953-816X
• DOI: 10.1111/j.1460-9568.2003.03051.x

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.