Transient receptor potential melastatin 4 channel (TRPM4)

The Transient receptor potential melastatin 4 (TRPM4) channel is a calcium-activated, non-selective cation channel that plays a critical role in regulating the membrane potential of various cell types (UniProt, Q8TD43). Unlike many other TRP channels, TRPM4 is impermeable to calcium but allows the flow of monovalent cations like sodium and potassium, thereby modulating the driving force for calcium entry (PubMed, 12730592). It is widely expressed in tissues including the heart, pancreas, and brain, where it contributes to cardiac conduction, insulin secretion, and the inflammatory response (NCBI Gene, 54795). In pathological conditions such as ischemic stroke, TRPM4 is upregulated and associates with the sulfonylurea receptor 1 (SUR1) to form a complex that mediates catastrophic cell swelling and cerebral edema (PubMed, 16604191). Consequently, TRPM4 has emerged as a promising therapeutic target for neurological injuries and certain cancers, such as prostate cancer, where its overexpression is linked to tumor progression (PubMed, 25907653). Pharmacological inhibition, notably by drugs like glibenclamide or research tools like 9-phenanthrol, aims to mitigate tissue damage and restore normal physiological signaling.

Other names

Melastatin-4TRPM4BCalcium-activated non-selective cation channel 1hTRPM4LTrpC4

TRPM4 acts as a calcium-activated non-selective cation channel that conducts monovalent cations (Na+, K+) but is impermeable to Ca2+. Drugs targeting TRPM4 typically act as inhibitors to prevent excessive membrane depolarization, which in pathological states like stroke leads to cytotoxic edema and cell death. In cardiac tissue, modulation of TRPM4 aims to correct conduction abnormalities caused by gain-of-function or loss-of-function mutations.