Serotonin activation of a cyclic AMP-dependent sodium current in an identified neuron from Helisoma trivolvis.
The mechanisms by which neurotransmitters regulate neurite extension and growth cone motility have been extensively studied using identified Helisoma neurons regenerating in cell culture. Specific neurons, such as buccal neuron B19, display a complex response to the addition of 5-HT involving the generation of action potentials, influx of extracellular calcium, and cessation of neurite extension and growth cone motility. While several studies have addressed the role of calcium in this cascade, little is known about the mechanism underlying the 5-HT-induced excitation of neuron B19. Therefore, we have begun to characterize the ion currents, receptors, and second messengers involved in the 5-HT-dependent depolarization of B19. Exposure of B19 to 5-HT resulted in the activation of a maintained inward current. Ion substitution experiments revealed that this current was carried mainly by sodium ions. The use of 8-bromo-cAMP, forskolin, or the phosphodiesterase inhibitor isobutyl methylxanthine (IBMX) to increase intracellular cAMP levels all resulted in inward current activation in the absence of 5-HT. Moreover, preloading the neuron with 8-bromo-cAMP was sufficient to prevent further current activation by 5-HT. In addition, the IBMX-activated current was greatly enhanced when induced in the presence of 5-HT. Protein kinase inhibitors failed to prevent 5-HT activation of sodium current, suggesting that cAMP may directly activate the current, independent of phosphorylation. Pharmacological experiments showed the B19 5-HT receptor has an EC50 of approximately 10(-7) M and can be activated by various indole analogs of 5-HT. Furthermore, methysergide displayed partial agonist activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Price
C J
CJ
Department of Zoology, University of Alberta, Edmonton, Canada.
Goldberg
J I
JI
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004553:Electric Conductivity / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008784:Methysergide / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D012908:Snails; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*
D015222:Sodium Channels; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012701:Serotonin; D000242:Cyclic AMP; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; D008784:Methysergide