A study of the mechanism of Ca2+ current inhibition produced by serotonin in rat dorsal raphe neurons

• Published in: The Journal of neuroscience Vol. 11; no. 11; pp. 3594 - 3609
• Main Authors: Penington, NJ, Kelly, JS, Fox, AP
• Format: Journal Article
• Language: English
• Published: Washington, DC Soc Neuroscience 01.11.1991; Society for Neuroscience
• Subjects: Animals; Biological and medical sciences; Calcium - antagonists & inhibitors; Calcium - physiology; Central nervous system; Dihydropyridines - pharmacology; Electrophysiology; Fundamental and applied biological sciences. Psychology; Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology; Guanosine Diphosphate - analogs & derivatives; Guanosine Diphosphate - pharmacology; Mollusk Venoms - pharmacology; Neurons - physiology; omega-Conotoxin GVIA; Peptides, Cyclic - pharmacology; Raphe Nuclei - cytology; Raphe Nuclei - physiology; Rats; Second Messenger Systems - physiology; Serotonin - pharmacology; Thionucleotides - pharmacology; Vertebrates: nervous system and sense organs; Calcium; Rat; Serotonin; Rodentia; Central nervous system; Electrophysiology; Patch clamp method; Ionic current; Vertebrata; Mammalia; Neuromediator; Raphe nuclei; Brain (vertebrata)
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.11-11-03594.1991

Calcium currents and their modulation by 5-HT were studied using both whole-cell and single-channel patch-clamp techniques in acutely isolated adult rat dorsal raphe neurons. Evidence for three types of Ca channels (T, N, L) was obtained in both whole-cell and single-channel experiments. Approximately 4% of the total high-threshold Ca current (L-type) was sensitive to dihydropyridines (DHPs) while approximately 40% of the Ca current (N-type) was sensitive to omega-conotoxin (omega-CgTx). About 56% of the whole-cell current was insensitive to either DHPs or omega-CgTx and may thus represent a different kind of Ca current. 5-HT reduced raphe neuron Ca currents by approximately 50%, while slowing activation. 5-HT inhibited both omega-CgTx-sensitive and -insensitive Ca current. Inhibition by 5-HT was voltage dependent; prepulses to +80 mV lasting for 20 msec almost completely abolished the 5-HT-mediated inhibition. The voltage dependence of the response to 5-HT suggested that trains of action potentials might overcome the inhibition due to 5-HT. Trains of brief depolarizations were used to simulate action potentials; only about 5% of the 5-HT-induced inhibition was relieved by the trains. These results suggest that while large depolarizations could restore the Ca current inhibited by 5-HT, physiological stimuli, such as trains of action potentials, could not. The action of 5-HT was made irreversible by inclusion of GTP-gamma-S in the patch pipette, suggesting a G-protein mediation of the response to 5-HT.