Novel form of LTD induced by transient, partial inhibition of the Na,K-pump in rat hippocampal CA1 cells.
We tested the hypothesis that transient, partial inhibition of the Na,K-pumps could produce lasting effects on synaptic efficacy in brain tissue by applying a low concentration of the ouabain analogue, dihydroouabain (DHO), to hippocampal slices for 15 min and studying the effects on field excitatory postsynaptic potentials (fEPSPs). DHO caused a suppression of fEPSPs during the application period, but this recovered only partially, to approximately 80% of control levels, after washout lasting as long as 2 h. The lasting suppression had several properties in common with low-frequency stimulation induced long-term depression (LFS-LTD), including an ability to depotentiate long-term potentiated responses. However, DHO-LTD was insensitive to blockade of N-methyl-d-aspartate or mGlu receptors or to inhibitors of protein kinase C or p38 MAP kinase. DHO-LTD did not co-occlude with LFS-LTD and therefore appears to represent a novel form of LTD. Interestingly, DHO-LTD could be prevented by pretreating slices with iberiotoxin, the selective blocker of large, Ca(2+)-dependent K+ channels ("big K," BK channels), although this toxin did not affect basal fEPSPs. Certain pathological conditions, including hypoxia and ischemia, are associated with a decrease in Na,K-pump activity and hence DHO-LTD may serve as a model for the effects on neuronal function in these conditions.
Reich
Christian G
CG
Department of Physiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Mason
Susanne E
SE
Alger
Bradley E
BE
D000818:Animals; D004347:Drug Interactions; D004558:Electric Stimulation; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005071:Evoked Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D010042:Ouabain / Q000031:analogs & derivatives* / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000502:physiology*; D013997:Time Factors
D004791:Enzyme Inhibitors; D007093:Imidazoles; D007211:Indoles; D008301:Maleimides; D010455:Peptides; D010880:Piperidines; D011720:Pyrazoles; D011725:Pyridines; C000977:dihydroouabain; C103505:AM 251; D010042:Ouabain; C064719:iberiotoxin; D000254:Sodium-Potassium-Exchanging ATPase; C088060:bisindolylmaleimide; C093642:SB 203580