Transient receptor potential cation channel subfamily M member 4 (TRPM4) (TRPM4)

Transient receptor potential cation channel subfamily M member 4 (TRPM4) is a calcium-activated, non-selective cation channel that conducts monovalent ions such as sodium and potassium while remaining impermeable to calcium [NIH, Wikipedia]. It is a critical regulator of membrane potential in a wide variety of tissues, including the heart, pancreas, and immune system [MedlinePlus, NIH]. By modulating the electrical gradient across the cell membrane, TRPM4 indirectly controls the driving force for calcium entry, thereby influencing intracellular calcium signaling and downstream cellular responses [NIH, Guide to Pharmacology]. In the cardiovascular system, TRPM4 is essential for maintaining normal cardiac rhythm, and mutations in the gene are linked to hereditary conduction disorders like Brugada syndrome and progressive heart block [MedlinePlus, NIH]. Beyond its physiological roles, TRPM4 is frequently overexpressed in various malignancies, including prostate and breast cancers, where it promotes hallmark features such as increased cell migration, invasion, and proliferation [NIH]. It also plays a significant role in the pathophysiology of central nervous system injuries, such as stroke and traumatic brain injury, where its activation contributes to cerebral edema and neuronal death [NIH]. Pharmacological modulation of TRPM4, particularly through inhibitors like glibenclamide (glyburide) and 9-phenanthrol, is currently being investigated as a therapeutic strategy for treating neurological emergencies and preventing cancer metastasis [NIH, Guide to Pharmacology]. However, the widespread expression of TRPM4 poses challenges for achieving tissue-specific effects and avoiding potential side effects related to cardiac and metabolic functions [NIH].

Other names

TRPM4PFHB1BTRPM4BLTrpC4Melastatin-4EKVP6Transient receptor potential melastatin member 4

Inhibition of the TRPM4 channel to prevent membrane depolarization and modulate calcium signaling [NIH, Guide to Pharmacology].