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A glibenclamide-sensitive TRPM4-mediated component of CA1 excitatory postsynaptic potentials appears in experimental

Brenna C Fearey1,2, Lars Binkle3, Daniel Mensching3

  • 1Institute of Synaptic Physiology, ZMNH, University Medical Center Hamburg-Eppendorf, Falkenried, 94 20251, Hamburg, Germany.

Scientific Reports
|April 10, 2022
PubMed

Insights

Transient receptor potential melastatin 4 (TRPM4) channels are not crucial for normal brain function but are upregulated in experimental autoimmune encephalomyelitis (EAE). Glibenclamide-sensitive TRPM4 activity boosts excitatory postsynaptic responses during EAE.

Area of Science:

  • Neuroscience
  • Ion Channel Physiology
  • Neuroimmunology

Background:

  • Transient receptor potential melastatin 4 (TRPM4) channels are implicated in multiple sclerosis (MS) and neuronal cell death.
  • TRPM4 channels conduct monovalent cations and are activated by intracellular calcium.
  • TRPM4's role in hippocampal excitatory synaptic transmission remains unclear.

Purpose of the Study:

  • To investigate the role of TRPM4 in hippocampal excitatory synaptic transmission.
  • To determine if TRPM4 contributes to synaptic alterations in the experimental autoimmune encephalomyelitis (EAE) model of MS.

Main Methods:

  • Electrophysiology and single-spine calcium imaging in hippocampal slices.
  • Utilized TRPM4 antagonists (9-phenanthrol, glibenclamide) and TRPM4 knockout mice.
  • Compared synaptic transmission in healthy mice versus EAE mice.

Main Results:

  • TRPM4 antagonists had no effect on synaptic transmission in healthy mice.
  • Glibenclamide, but not 9-phenanthrol, reduced excitatory synaptic potentials in EAE mice.
  • This glibenclamide effect was absent in EAE mice lacking TRPM4, indicating TRPM4 upregulation.

Conclusions:

  • TRPM4 plays a minimal role in basal hippocampal synaptic transmission.
  • A glibenclamide-sensitive TRPM4-mediated contribution to excitatory postsynaptic responses is upregulated during the acute phase of EAE.
  • TRPM4 is a potential therapeutic target for MS-related synaptic dysfunction.

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