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

  title={The potassium channel modulator flupirtine shifts the frequency–response function of hippocampal synapses to favour LTD in mice},
  author={Shahnaz Christina Azad and Matthias Eder and Wanda Simon and Gerhard Hapfelmeier and Hans-Ulrich Dodt and Walter Zieglgänsberger and Gerhard Rammes},
  journal={Neuroscience Letters},
The Kv7 potassium channel activator flupirtine affects clinical excitability parameters of myelinated axons in isolated rat sural nerve
Assessment of measures of excitability that are altered in the myelinated axons of patients with peripheral nerve disorders indicates that neuropathies with abnormal nerve excitability parameters corresponding to those affected by flupirtine may benefit from activation of axonal Kv7 potassium channels.
Calcium Signaling During Brain Aging and Its Influence on the Hippocampal Synaptic Plasticity.
  • Ashok Kumar
  • Biology
    Advances in experimental medicine and biology
  • 2020
Assessing various Ca2+ sources and the influence of aging on Ca2- sources and synaptic plasticity in the hippocampus takes a specific perspective, integrating the knowledge of the complexity of age-related alterations in neuronal Ca2+.
Calcium homeostasis and modulation of synaptic plasticity in the aged brain
Evidence is reviewed for a shift in the sources of intracellular Ca2+ characterized by a diminished role for N‐methyl‐D‐aspartate receptors and an increased role for intrACEllular stores and voltage‐dependent Ca2+, resulting in a functional lesion of the hippocampus.
Modulation of the extinction of fear learning
Calcium Signaling
Calcium signaling and its interacting networks are involved in mediating numerous processes including gene expression, excitation-contraction coupling, stimulus-secretion coupling, synaptic
In Vivo Profile of ICA-27243 [N-(6-Chloro-pyridin-3-yl)-3,4-difluoro-benzamide], a Potent and Selective KCNQ2/Q3 (Kv7.2/Kv7.3) Activator in Rodent Anticonvulsant Models
It is suggested that selective KCNQ2/Q3 opening activity in the absence of effects onKCNQ3/Q5 or GABA-activated channels may be sufficient for broad-spectrum antiepileptic activity in rodents.


Flupirtine shows functional NMDA receptor antagonism by enhancing Mg2+ block via activation of voltage independent potassium channels
A global model was developed in which flupirtine stabilizes the resting membrane potential by activating inwardly rectifying K+ channels, thus indirectly inhibiting the activation of NMDA receptors.
Influence of flupirtine on a G‐protein coupled inwardly rectifying potassium current in hippocampal neurones
Results show that in cultured hippocampal neurones flupirtine activates an inwardly rectifying potassium current and that a PTX‐sensitive G‐protein is involved in the transduction mechanism.
An experimental test of the role of postsynaptic calcium levels in determining synaptic strength using perirhinal cortex of rat
The lack of plasticity that occurs at the transition between LTD and LTP is due to the lack of induction of both of these processes and also suggests that these two processes are induced independently of one another.
Role of NMDA Receptor Subtypes in Governing the Direction of Hippocampal Synaptic Plasticity
Using hippocampal slice preparations, it is shown that selectively blocking NMDARs that contain the NR2B subunit abolishes the induction of LTD but not LTP, demonstrating that distinct N MDAR subunits are critical factors that determine the polarity of synaptic plasticity.
Induction of long‐term potentiation at spinal synapses by noxious stimulation or nerve injury
The natural non‐synchronized discharge patterns that are evoked by noxious stimulation may induce LTP and this new form of LTP may be an underlying mechanism of afferent induced hyperalgesia, which is suppressed by tonically active supraspinal descending systems.
Bidirectional long-term modification of synaptic effectiveness in the adult and immature hippocampus
  • SM DudekMF Bear
  • Biology
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1993
To address the question of whether depressed synapses can still be potentiated and vice versa, LTP was saturated with repeated high- frequency tetani, and then LTD was induced with low-frequency stimulation (LFS), indicating that the same synapses whose transmission had been depressed by LFS were capable of subsequently supporting potentiation.
Dynamical model of long-term synaptic plasticity
A dynamical model reproduces the spike time-dependent plasticity of excitatory synapses as a function of relative timing between pre- and postsynaptic events, as observed in recent experiments.
Perceptual Correlates of Nociceptive Long-Term Potentiation and Long-Term Depression in Humans
HFS and LFS stimulus protocols that induce LTP or LTD in spinal nociceptive pathways in animal experiments led to similar LTP- and LTD-like changes in human pain perception mediated by the conditioned pathway, including secondary hyperalgesia and allodynia in adjacent skin.
Bidirectional synaptic plasticity correlated with the magnitude of dendritic calcium transients above a threshold.
Estimates of the threshold Ca(2+) level for LTD and for the transition from LTD to LTP may assist in constraining the molecular details of such models as well as support a class of models in which failure of Ca( 2+) transients to affect transmission may arise.