The potassium channel modulator flupirtine shifts the frequency-response function of hippocampal synapses to favour LTD in mice

Shahnaz Christina Azad, Matthias Eder, Wanda Simon, Gerhard Hapfelmeier, Hans Ulrich Dodt, Walter Zieglgänsberger, Gerhard Rammes

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Flupirtine is a centrally acting nonopioid analgesic with muscle-relaxant properties. Flupirtine has been found to activate inwardly rectifying potassium conductances and hence to indirectly inhibit the activation of NMDA receptors. NMDA receptor activation is crucial for the induction of long-term potentiation (LTP) of synaptic transmission, which is considered as cellular correlate of learning and memory and of central sensitization in chronic pain states. Although flupirtine has been widely used for the management of pain, its effects on synaptic plasticity have not yet been investigated. We, therefore, performed extracellular and whole-cell patch-clamp recordings in hippocampal slices of mice to examine the effects of flupirtine on synaptic plasticity and neuronal membrane properties. Excitatory postsynaptic potentials (EPSPs) in the CA1 region were evoked alternately by stimulating two independent Schaffer collateral-commissural inputs. LTP and long-term depression (LTD) were induced by different stimulation paradigms (100 Hz, 10 Hz, 5 Hz, and 1 Hz). Flupirtine (30 μM) diminished the degree of LTP and enhanced LTD. This effect is most likely due to the hyperpolarization of CA1 pyramidal neurons and the reduction of their input resistance found after application of flupirtine. The observed effects on synaptic strength could underly the beneficial effects of flupirtine on different types of chronic pain.

Original languageEnglish
Pages (from-to)186-190
Number of pages5
JournalNeuroscience Letters
Volume370
Issue number2-3
DOIs
StatePublished - 11 Nov 2004

Keywords

  • Analgesic
  • Flupirtine
  • Hippocampus
  • Long-term depression
  • Long-term potentiation
  • Synaptic plasticity

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