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Exploring the role of TRPM4 in calcium-dependent triggered activity and cardiac arrhythmias

Andy Pironet1, Frone Vandewiele1, Rudi Vennekens1

  • 1Laboratory of Ion Channel Research, VIB Centre for Brain and Disease Research, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.

The Journal of Physiology
|May 2, 2023
PubMed

Insights

Transient Receptor Potential Melastatin 4 (TRPM4) channels are implicated in cardiac arrhythmias by disrupting calcium (Ca2+) homeostasis. TRPM4 may translate increased intracellular Ca2+ into cellular excitation, contributing to arrhythmias.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Physiology

Background:

  • Cardiac arrhythmias are a significant health risk, often difficult to predict, prevent, and treat.
  • Disturbed calcium (Ca2+) homeostasis in cardiac muscle cells is a key mechanism underlying arrhythmias.
  • Transient Receptor Potential Melastatin 4 (TRPM4) channels are Ca2+-activated non-selective cation channels linked to Ca2+-induced arrhythmias.

Purpose of the Study:

  • To review the role of TRPM4 channels in Ca2+-dependent cardiac arrhythmias.
  • To explore how TRPM4 contributes to translating intracellular Ca2+ increases into membrane depolarization and cellular excitability.

Main Methods:

  • Review of existing data from genetically modified mouse models.
  • Analysis of human patient mutations associated with TRPM4.
  • Consideration of in vivo studies using TRPM4 blocking compounds.

Main Results:

  • Evidence from genetic studies in mice and humans supports TRPM4's involvement in arrhythmias.
  • TRPM4 channel activity is linked to increased cellular excitability and membrane depolarization.
  • Pharmacological inhibition of TRPM4 shows potential in managing arrhythmias.

Conclusions:

  • TRPM4 channels play a critical role in Ca2+-dependent cardiac arrhythmias.
  • Understanding TRPM4 function provides insights into arrhythmia mechanisms.
  • TRPM4 represents a potential therapeutic target for treating cardiac arrhythmias.
Keywords:
TRPM4arrhythmiacalcium‐dependent triggered activityion channelstransient receptor potential ion channels

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