Staurosporine impairs both short-term and long-term potentiation in the dentate gyrus in vitro.
The present study shows that the protein kinase inhibitor staurosporine impairs the transient (< 60 min) potentiation (short-term potentiation) evoked by a weak tetanus to about the same extent as the more stable potentiation (long-term potentiation) evoked by a strong tetanus. This effect on short-term and long-term potentiation was seen both as a reduced magnitude and an increased decay rate, the latter being increased by about 50% compared to that seen under normal conditions. Comparison with potentiations evoked at different strengths in control solution suggested that much, but not all, of the increased decay rate observed in the presence of staurosporine could be explained by an impared induction. Staurosporine did not affect the N-methyl-D-aspartate-mediated field excitatory postsynaptic potential evoked by low-frequency stimulation or the magnitude of N-methyl-D-aspartate-mediated currents during high-frequency tetanization. This result suggests that the induction is impaired at a stage not related to the N-methyl-D-aspartate-mediated calcium influx. The present results suggest that short-term and long-term potentiation cannot be separated on the basis of protein kinase dependence. They do not support the common notion that short-term and long-term potentiation are mechanistically separate entities. Instead, the results support the view that long-term potentiation has a variable duration/stability dependent on the induction conditions and that protein kinase activation, via an action on induction mechanisms, contributes to its stabilization.
Hanse
E
E
Department of Physiology, University of Göteborg, Sweden.
Gustafsson
B
B
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D019311:Staurosporine
D000470:Alkaloids; D047428:Protein Kinase Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D011494:Protein Kinases; D011493:Protein Kinase C; D019311:Staurosporine