Novel form of LTD induced by transient, partial inhibition of the Na,K-pump in rat hippocampal CA1 cells

J Neurophysiol. 2004 Jan;91(1):239-47. doi: 10.1152/jn.00722.2003.


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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Drug Interactions
  • Electric Stimulation
  • Electrophysiology
  • Enzyme Inhibitors / pharmacology
  • Evoked Potentials / physiology
  • Hippocampus / cytology*
  • Imidazoles / pharmacology
  • In Vitro Techniques
  • Indoles / pharmacology
  • Long-Term Synaptic Depression / drug effects
  • Long-Term Synaptic Depression / physiology*
  • Male
  • Maleimides / pharmacology
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neurons / classification
  • Neurons / drug effects
  • Neurons / physiology*
  • Ouabain / analogs & derivatives*
  • Ouabain / pharmacology
  • Peptides / pharmacology
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / physiology*
  • Time Factors


  • Enzyme Inhibitors
  • Imidazoles
  • Indoles
  • Maleimides
  • Peptides
  • Piperidines
  • Pyrazoles
  • Pyridines
  • dihydroouabain
  • AM 251
  • Ouabain
  • iberiotoxin
  • Sodium-Potassium-Exchanging ATPase
  • bisindolylmaleimide
  • SB 203580