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

Cardiac arrhythmias pose a major threat to a patient's health, yet prove to be often difficult to predict, prevent and treat. A key mechanism in the occurrence of arrhythmias is disturbed Ca²⁺ homeostasis in cardiac muscle cells. As a Ca²⁺-activated non-selective cation channel, TRPM4 has been linked to Ca²⁺-induced arrhythmias, potentially contributing to translating an increase in intracellular Ca²⁺ concentration into membrane depolarisation and an increase in cellular excitability. Indeed, evidence from genetically modified mice, analysis of mutations in human patients and the identification of a TRPM4 blocking compound that can be applied in vivo further underscore this hypothesis. Here, we provide an overview of these data in the context of our current understanding of Ca²⁺-dependent arrhythmias.