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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Sep;84(17):6307–6311. doi: 10.1073/pnas.84.17.6307

Augmentation of bursting pacemaker activity by egg-laying hormone in Aplysia neuron R15 is mediated by a cyclic AMP-dependent increase in Ca2+ and K+ currents.

E S Levitan, R H Kramer, I B Levitan
PMCID: PMC299060  PMID: 2819871

Abstract

Release of the neuropeptide egg-laying hormone (ELH) from Aplysia bag cell neurons augments the endogenous bursting pacemaker activity of neuron R15. We have studied the ionic mechanisms underlying the effect of ELH in voltage-clamped R15 neurons. Both electrical discharge of the bag cells, which releases endogenous ELH, and application of synthetic ELH on cell R15 result in an increase in two discrete ionic currents. One of these currents activates with hyperpolarization, reverses near the K+ equilibrium potential, is sensitive to the external K+ concentration, and is blocked by addition of 5 mM Rb+ or 1 mM Ba2+ to the bathing medium. This current appears to be identical to the inwardly rectifying K+ current IR. The other current activates with depolarization and is blocked by replacement of external Ca2+ with Co2+ or Mn2+. This current appears to be a voltage-gated Ca2+ current ICa. Both ICa and IR in R15 have previously been shown to be enhanced by the neurotransmitter serotonin, acting via intracellular cyclic AMP. We now report that increasing cyclic AMP in R15, by applying either serotonin or the adenylate cyclase activator forskolin together with a phosphodiesterase inhibitor, mimics and occludes the action of ELH on neuron R15. Furthermore, application of ELH increases the cyclic AMP content of single R15 neurons, as measured by radioimmunoassay. Finally, the effects of ELH are potentiated by a phosphodiesterase inhibitor. These results suggest that ELH augments bursting activity in R15 by causing cyclic AMP-mediated increases in IR and ICa.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams D. J., Gage P. W. Ionic currents in response to membrane depolarization in an Aplysia neurone. J Physiol. 1979 Apr;289:115–141. doi: 10.1113/jphysiol.1979.sp012728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adams W. B., Benson J. A. The generation and modulation of endogenous rhythmicity in the Aplysia bursting pacemaker neurone R15. Prog Biophys Mol Biol. 1985;46(1):1–49. doi: 10.1016/0079-6107(85)90011-2. [DOI] [PubMed] [Google Scholar]
  3. Adams W. B., Levitan I. B. Voltage and ion dependences of the slow currents which mediate bursting in Aplysia neurone R15. J Physiol. 1985 Mar;360:69–93. doi: 10.1113/jphysiol.1985.sp015604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Adams W. B., Parnas I., Levitan I. B. Mechanism of long-lasting synaptic inhibition in Aplysia neuron R15. J Neurophysiol. 1980 Dec;44(6):1148–1160. doi: 10.1152/jn.1980.44.6.1148. [DOI] [PubMed] [Google Scholar]
  5. Ascher P. Inhibitory and excitatory effects of dopamine on Aplysia neurones. J Physiol. 1972 Aug;225(1):173–209. doi: 10.1113/jphysiol.1972.sp009933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Barker J. L., Ifshin M. S., Gainer N. Studies on bursting pacemaker potential activity in molluscan neurons. III. Effects of hormones. Brain Res. 1975 Feb 14;84(3):501–513. doi: 10.1016/0006-8993(75)90768-4. [DOI] [PubMed] [Google Scholar]
  7. Benson J. A., Levitan I. B. Serotonin increases an anomalously rectifying K+ current in the Aplysia neuron R15. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3522–3525. doi: 10.1073/pnas.80.11.3522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Branton W. D., Arch S., Smock T., Mayeri E. Evidence for mediation of a neuronal interaction by a behaviorally active peptide. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5732–5736. doi: 10.1073/pnas.75.11.5732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dekin M. S., Richerson G. B., Getting P. A. Thyrotropin-releasing hormone induces rhythmic bursting in neurons of the nucleus tractus solitarius. Science. 1985 Jul 5;229(4708):67–69. doi: 10.1126/science.3925552. [DOI] [PubMed] [Google Scholar]
  10. Drummond A. H., Benson J. A., Levitan I. B. Serotonin-induced hyperpolarization of an indentified Aplysia neuron is mediated by cyclic AMP. Proc Natl Acad Sci U S A. 1980 Aug;77(8):5013–5017. doi: 10.1073/pnas.77.8.5013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Giller E., Jr, Schwartz J. H. Choline acetyltransferase in identified neurons of abdominal ganglion of Aplysia californica. J Neurophysiol. 1971 Jan;34(1):93–107. doi: 10.1152/jn.1971.34.1.93. [DOI] [PubMed] [Google Scholar]
  12. Gorman A. L., Hermann A., Thomas M. V. Ionic requirements for membrane oscillations and their dependence on the calcium concentration in a molluscan pace-maker neurone. J Physiol. 1982 Jun;327:185–217. doi: 10.1113/jphysiol.1982.sp014227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gunning R. Increased numbers of ion channels promoted by an intracellular second messenger. Science. 1987 Jan 2;235(4784):80–82. doi: 10.1126/science.2432659. [DOI] [PubMed] [Google Scholar]
  14. Hermann A., Gorman A. L. Effects of tetraethylammonium on potassium currents in a molluscan neurons. J Gen Physiol. 1981 Jul;78(1):87–110. doi: 10.1085/jgp.78.1.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kirk M. D., Scheller R. H. Egg-laying hormone of Aplysia induces a voltage-dependent slow inward current carried by Na+ in an identified motoneuron. Proc Natl Acad Sci U S A. 1986 May;83(9):3017–3021. doi: 10.1073/pnas.83.9.3017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kramer R. H., Zucker R. S. Calcium-induced inactivation of calcium current causes the inter-burst hyperpolarization of Aplysia bursting neurones. J Physiol. 1985 May;362:131–160. doi: 10.1113/jphysiol.1985.sp015667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Levitan I. B. Adenylate cyclase in isolated Helix and Aplysia neuronal cell bodies: stimulation by serotonin and peptide-containing extract. Brain Res. 1978 Oct 13;154(2):404–408. doi: 10.1016/0006-8993(78)90714-x. [DOI] [PubMed] [Google Scholar]
  18. Levitan I. B., Norman J. Different effects of cAMP and cGMP derivatives on the activity of an identified neuron: biochemical and electrophysiological analysis. Brain Res. 1980 Apr 14;187(2):415–429. doi: 10.1016/0006-8993(80)90212-7. [DOI] [PubMed] [Google Scholar]
  19. Lewis D. V., Evans G. B., Wilson W. A. Dopamine reduces slow outward current and calcium influx in burst-firing neuron R15 of Aplysia. J Neurosci. 1984 Dec;4(12):3014–3020. doi: 10.1523/JNEUROSCI.04-12-03014.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lotshaw D. P., Levitan E. S., Levitan I. B. Fine tuning of neuronal electrical activity: modulation of several ion channels by intracellular messengers in a single identified nerve cell. J Exp Biol. 1986 Sep;124:307–322. doi: 10.1242/jeb.124.1.307. [DOI] [PubMed] [Google Scholar]
  21. Mayeri E., Brownell P., Branton W. D., Simon S. B. Multiple, prolonged actions of neuroendocrine bag cells on neurons in Aplysia. I. Effects on bursting pacemaker neurons. J Neurophysiol. 1979 Jul;42(4):1165–1184. doi: 10.1152/jn.1979.42.4.1165. [DOI] [PubMed] [Google Scholar]
  22. Mayeri E., Rothman B. S., Brownell P. H., Branton W. D., Padgett L. Nonsynaptic characteristics of neurotransmission mediated by egg-laying hormone in the abdominal ganglion of Aplysia. J Neurosci. 1985 Aug;5(8):2060–2077. doi: 10.1523/JNEUROSCI.05-08-02060.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Parnas I., Strumwasser F. Mechanisms of long-lasting inhibition of a bursting pacemaker neuron. J Neurophysiol. 1974 Jul;37(4):609–620. doi: 10.1152/jn.1974.37.4.609. [DOI] [PubMed] [Google Scholar]
  24. Rothman B. S., Weir G., Dudek F. E. Egg-laying hormone: direct action on the ovotestis of Aplysia. Gen Comp Endocrinol. 1983 Oct;52(1):134–141. doi: 10.1016/0016-6480(83)90166-1. [DOI] [PubMed] [Google Scholar]
  25. Seamon K. B., Padgett W., Daly J. W. Forskolin: unique diterpene activator of adenylate cyclase in membranes and in intact cells. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3363–3367. doi: 10.1073/pnas.78.6.3363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Stuart D. K., Strumwasser F. Neuronal sites of action of a neurosecretory peptide, egg-laying hormone, in Aplysia californica. J Neurophysiol. 1980 Feb;43(2):499–519. doi: 10.1152/jn.1980.43.2.499. [DOI] [PubMed] [Google Scholar]

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