title: Inhibitor of adenosine 3':5'-monophosphate-dependent protein kinase blocks presynaptic facilitation in Aplysia.
abstract: Sensitization of the gill withdrawal reflex results from presynaptic facilitation at the excitatory synapses made by sensory neurons on gill motor neurons. Facilitation is accompanied by an increase in the duration of the action potential in sensory cells because of the depression of a K+ current. This results in an increasd influx of CA2+ and a greater release of transmitter from sensory neurons. There is evidence that serotonin is the facilitating transmitter and that the depression of the K+ current by serotonin mediated by cAMP-dependent protein phosphorylation. To test further the role of the cAMP-dependent protein kinase and of protein phosphorylation in sensitization, we have attempted to prevent or reverse the development of the electrophysiological correlates that accompany sensitization. We have pressure-injected sensory neurons with a specific and a stable protein inhibitor of the cAMP-dependent protein kinase both before and after the application of serotonin or the activation of the facilitator neurons. The increase in spike broadening that accompanies facilitation was prevented or diminished by injection of the inhibitor.  Moreover, injection of the inhibitor could reverse fully the developed spike broadening produced by prior application of serotonin. These observations strenthen the evidence for the involvement of protein phosphorylation in presynaptic facilitation. Phosphorylation of the substrate protein evidently is quite labile and does not persist after the kinase is inhibited. Thus, the time course of short term sensitization appears to be determined by an active kinase. We think that it is likely that the mechanism for maintaining the kinase in an active form resides in the slow decay of the cAMP produced by the action of serotonin or the facilitator neurons on the sensory cells.
mesh_terms: D000818:Animals; D001048:Aplysia / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D012701:Serotonin / Q000494:pharmacology; D013569:Synapses / Q000502:physiology*
chemical_list: D047428:Protein Kinase Inhibitors; D012701:Serotonin; D000242:Cyclic AMP; D011188:Potassium; D002118:Calcium