A study of the mechanism of Ca2+ current inhibition produced by serotonin in rat dorsal raphe neurons.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Penington
N J
NJ
Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637.
Kelly
J S
JS
Fox
A P
AP
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology; D004594:Electrophysiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D008978:Mollusk Venoms / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology / Q000502:physiology*; D051381:Rats; D015290:Second Messenger Systems / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D004095:Dihydropyridines; D008978:Mollusk Venoms; D010456:Peptides, Cyclic; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D012701:Serotonin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C023427:guanosine 5'-O-(2-thiodiphosphate); D020866:omega-Conotoxin GVIA; D002118:Calcium