Metaplastic effect of apamin on LTP and paired-pulse facilitation.
In area CA1 of hippocampal slices, a single 1-sec train of 100-Hz stimulation generally triggers a short-lasting long-term potentiation (S-LTP) of 1-2 h. Here, we found that when such a train was applied 45 min after application of the small conductance Ca(2+)-activated K(+ )(SK) channel blocker apamin, it induced a long-lasting LTP (L-LTP) of several hours, instead of an S-LTP. Apamin-induced SK channel blockage is known to resist washing. Nevertheless, the aforementioned effect is not a mere delayed effect; it is metaplastic. Indeed, when a single train was delivered to the Schaffer's collaterals during apamin application, it induced an S-LTP, like in the control situation. At the moment of this LTP induction (15th min of apamin application), the SK channel blockage was nevertheless complete. Indeed, at that time, under the influence of apamin, the amplitude of the series of field excitatory postsynaptic potentials (fEPSPs) triggered by a stimulation train was increased. We found that the metaplastic effect of apamin on LTP was crucially dependent on the NO-synthase pathway, whereas the efficacy of the NMDA receptors was not modified at the time of its occurrence. We also found that apamin produced an increase in paired-pulse facilitation not during, but after, the application of the drug. Finally, we found that the induction of each of these two metaplastic phenomena was mediated by NMDA receptors. A speculative unitary hypothesis to explain these phenomena is proposed.
Ris
Laurence
L
Laboratory of Neurosciences, University of Mons-Hainaut, Mons, Belgium.
Capron
Brigitte
B
Sclavons
Coralie
C
Liégeois
Jean-François
JF
Seutin
Vincent
V
Godaux
Emile
E
D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011930:Reaction Time; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors
D016194:Receptors, N-Methyl-D-Aspartate; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin; D019001:Nitric Oxide Synthase