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Volume 17, Number 19, Issue of October 1, 1997 pp. 7237-7244
Copyright ©1997 Society for Neuroscience

Modulation of a cAMP/Protein Kinase A Cascade by Protein Kinase C in Sensory Neurons of Aplysia

Received June 30, 1997; accepted July 14, 1997.

Shuzo Sugita, Douglas A. Baxter, and John H. Byrne

Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, Texas 77225

The synaptic connections between the sensory neurons of Aplysia and their follower neurons have been used as a model system for examining the cellular mechanisms contributing to neuronal and synaptic plasticity. Recent studies suggest that at least two protein kinases, protein kinase A (PKA) and protein kinase C (PKC), contribute to serotonin (5-HT)-induced short-term facilitation. The interaction between these two kinase cascades has not been examined, however. Using electrophysiological and biochemical approaches, we examined possible interactions between PKA and PKC cascades. The results indicated that prolonged activation of PKC by preincubation with phorbol esters attenuated PKA-mediated actions of 5-HT, including increases in sensory neuron excitability and spike broadening in the presence of tetraethylammonium (TEA) and nifedipine. Although phorbol esters also attenuated increases in excitability by an analog of cAMP and small cardioactive peptide B (SCPB), the degree of attenuation was smaller. In addition, phorbol esters did not attenuate broadening of TEA spikes by the cAMP analog and SCPB. Thus, phorbol esters appeared specifically to attenuate aspects of the 5-HT activation of the cAMP/PKA cascade. Measurements of cAMP levels with radioimmunoassays revealed that phorbol esters did not attenuate 5-HT-induced cAMP synthesis, however. Finally, the results indicated that phorbol esters themselves induced a small but significant increase in excitability as well as an increase in the level of cAMP. Our results suggest that there is crosstalk between the PKC and PKA cascades. The mechanisms by which phorbol esters specifically attenuate 5-HT-induced activation of the cAMP/PKA cascade are not known, however.

Key words: Aplysia californica; protein kinase A; protein kinase C; cyclic AMP; crosstalk; synaptic facilitation; modulation; serotonin; sensory neurons; learning and memory




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