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TRPM4 Contributes to Subthreshold Membrane Potential Oscillations in Multiple Mouse Pacemaker Neurons.

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Transient Receptor Potential Melastatin 4 (TRPM4) channels contribute to rhythmic neuronal firing in the locus coeruleus (LC) and suprachiasmatic nucleus (SCN). This finding reveals TRPM4

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Physiology

Background:

  • Specific neurons exhibit rhythmic firing crucial for tonic excitation.
  • Locus Coeruleus (LC), Suprachiasmatic Nucleus (SCN), and Retrotrapezoid Nucleus (RTN) neurons show subthreshold oscillations driving action potentials.
  • LC and SCN oscillations involve NALCN and L-type calcium channels; RTN oscillations may involve TRPM4.

Purpose of the Study:

  • To investigate the role of Transient Receptor Potential Melastatin 4 (TRPM4) in subthreshold oscillations in mouse LC and SCN.
  • To determine if TRPM4 contributes to the pacemaker-like activity of these neurons.

Main Methods:

  • RNAscope in situ hybridization to detect Trpm4 transcripts in LC and SCN.
  • Whole-cell recordings in acute brain slices to analyze membrane potential oscillations.
  • Pharmacological inhibition of TRPM4 using 9-phenanthrol (9-pt) and CBA.
  • Whole-cell voltage clamp to assess inward currents.

Main Results:

  • Trpm4 transcripts were confirmed in both LC and SCN.
  • Voltage-dependent membrane potential oscillations were observed in LC and SCN neurons after action potential blockade.
  • TRPM4 blockers (9-pt, CBA) significantly inhibited these oscillations.
  • Inward currents in LC neurons were reduced by blocking L-type calcium channels and TRPM4.

Conclusions:

  • TRPM4 channels play a significant role in subthreshold membrane potential oscillations in mouse LC and SCN neurons.
  • TRPM4 provides a voltage-dependent, calcium-dependent cationic current that complements Na+ and Ca2+ currents in driving tonic neuronal firing.
  • This study implicates TRPM4 in the fundamental electrophysiological properties of key neuronal populations.