Abstract
Previous work has shown that serotonin induces an increase in membrane K+ conductance in Aplysia neuron R15 and that this response is mediated by cAMP. The present study examines the role of protein phosphorylation in the response to serotonin. A specific inhibitor of cAMP-dependent protein kinase was injected intracellularly into neuron R15. The injection blocked the serotonin-induced increase in K+ conductance completely for at least 4 hours. The blockage was selective because the cell's response to dopamine was not inhibited. Furthermore, the blockage was specifically produced by protein kinase inhibitor because injection of other proteins (alpha-bungarotoxin and bovine serum albumin) did not affect the serotonin response. The serotonin response recovered fully 5-13 hours after the injection, presumably as a result of intracellular proteolysis of the protein kinase inhibitor. The results indicate that protein phosphorylation is a necessary step in the process that leads to activation of K+ channels by serotonin in neuron R15.
Full text
PDF



Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Ashby C. D., Walsh D. A. Characterization of the interaction of a protein inhibitor with adenosine 3',5'-monophosphate-dependent protein kinases. I. Interaction with the catalytic subunit of the protein kinase. J Biol Chem. 1972 Oct 25;247(20):6637–6642. [PubMed] [Google Scholar]
- Bittar E. E., Demaille J., Fischer E. H., Schultz R. Mode of stimulation by injection of cyclic AMP and external acidification of the sodium efflux in barnacle muscle fibres. J Physiol. 1979 Nov;296:277–289. doi: 10.1113/jphysiol.1979.sp013005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blankenship J. E., Wachtel H., Kandel E. R. Ionic mechanisms of excitatory, inhibitory, and dual synaptic actions mediated by an identified interneuron in abdominal ganglion of Aplysia. J Neurophysiol. 1971 Jan;34(1):76–92. doi: 10.1152/jn.1971.34.1.76. [DOI] [PubMed] [Google Scholar]
- Castellucci V. F., Kandel E. R., Schwartz J. H., Wilson F. D., Nairn A. C., Greengard P. Intracellular injection of t he catalytic subunit of cyclic AMP-dependent protein kinase simulates facilitation of transmitter release underlying behavioral sensitization in Aplysia. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7492–7496. doi: 10.1073/pnas.77.12.7492. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Demaille J. G., Peters K. A., Fischer E. H. Isolation and properties of the rabbit skeletal muscle protein inhibitor of adenosine 3',5'-monophosphate dependent protein kinases. Biochemistry. 1977 Jul 12;16(14):3080–3086. doi: 10.1021/bi00633a006. [DOI] [PubMed] [Google Scholar]
- Deterre P., Paupardin-Tritsch D., Bockaert J., Gerschenfeld H. M. Role of cyclic AMP in a serotonin-evoked slow inward current in snail neurones. Nature. 1981 Apr 30;290(5809):783–785. doi: 10.1038/290783a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Drummond A. H., Bucher F., Levitan I. B. Distribution of serotonin and dopamine receptors in Aplysia tissues: analysis by [3H]LSD binding and adenylate cyclase stimulation. Brain Res. 1980 Feb 17;184(1):163–177. doi: 10.1016/0006-8993(80)90595-8. [DOI] [PubMed] [Google Scholar]
- Kaczmarek L. K., Jennings K. R., Strumwasser F., Nairn A. C., Walter U., Wilson F. D., Greengard P. Microinjection of catalytic subunit of cyclic AMP-dependent protein kinase enhances calcium action potentials of bag cell neurons in cell culture. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7487–7491. doi: 10.1073/pnas.77.12.7487. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaczmarek L. K., Jennings K., Strumwasser F. Neurotransmitter modulation, phosphodiesterase inhibitor effects, and cyclic AMP correlates of afterdischarge in peptidergic neurites. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5200–5204. doi: 10.1073/pnas.75.10.5200. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klein M., Kandel E. R. Mechanism of calcium current modulation underlying presynaptic facilitation and behavioral sensitization in Aplysia. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6912–6916. doi: 10.1073/pnas.77.11.6912. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kuo J. F., Greengard P. Cyclic nucleotide-dependent protein kinases. IV. Widespread occurrence of adenosine 3',5'-monophosphate-dependent protein kinase in various tissues and phyla of the animal kingdom. Proc Natl Acad Sci U S A. 1969 Dec;64(4):1349–1355. doi: 10.1073/pnas.64.4.1349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levitan I. B., Adams W. B. Cyclic AMP modulation of a specific ion channel in an identified nerve cell: possible role for protein phosphorylation. Adv Cyclic Nucleotide Res. 1981;14:647–653. [PubMed] [Google Scholar]
- 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]
- Maller J. L., Krebs E. G. Progesterone-stimulated meiotic cell division in Xenopus oocytes. Induction by regulatory subunit and inhibition by catalytic subunit of adenosine 3':5'-monophosphate-dependent protein kinase. J Biol Chem. 1977 Mar 10;252(5):1712–1718. [PubMed] [Google Scholar]
- Pellmar T. C. Ionic mechanism of a voltage-dependent current elicited by cyclic AMP. Cell Mol Neurobiol. 1981 Mar;1(1):87–97. doi: 10.1007/BF00736041. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilson W. A., Wachtel H. Prolonged inhibition in burst firing neurons: synaptic inactivation of the slow regenerative inward current. Science. 1978 Nov 17;202(4369):772–775. doi: 10.1126/science.715442. [DOI] [PubMed] [Google Scholar]