Sulfonylurea receptor 1-Transient receptor potential melastatin 4 channel complex (SUR1-TRPM4)

The Sulfonylurea receptor 1-Transient receptor potential melastatin 4 (SUR1-TRPM4) channel complex is a heteromeric, non-selective monovalent cation channel that plays a critical role in the pathophysiology of acute central nervous system (CNS) injuries [1, 6]. It is composed of four SUR1 subunits and four TRPM4 subunits, forming a hetero-octameric structure that is typically absent in the healthy brain but is transcriptionally upregulated de novo in neurons, astrocytes, and endothelial cells following ischemic stroke, traumatic brain injury, or spinal cord trauma [3, 5, 6]. Activation of the channel by intracellular calcium and depleted ATP levels leads to a massive influx of sodium ions, causing cell depolarization, cytotoxic edema, and eventually oncotic (necrotic) cell death [1, 6]. This process is a major driver of blood-brain barrier breakdown and the formation of vasogenic edema in injured neural tissue [5, 7]. Pharmacological targeting of the SUR1 subunit with drugs like glibenclamide (glyburide) inhibits channel opening, thereby mitigating cerebral edema and secondary tissue damage [3, 9]. Clinical trials, such as the GAMES-RP and CHARM studies, have evaluated the efficacy of glibenclamide in reducing brain swelling and improving neurological outcomes, establishing the SUR1-TRPM4 complex as a significant therapeutic target in neurocritical care [6, 10].

Other names

SUR1-regulated NCCa-ATP channelSUR1-NCCa-ATP channelNon-selective cation channel regulated by Ca2+ and ATPNC(Ca-ATP) channel

Glibenclamide binds to the SUR1 subunit of the SUR1-TRPM4 complex, reducing the open channel probability and inhibiting the influx of monovalent cations (primarily sodium), which prevents osmotic swelling, cytotoxic edema, and subsequent oncotic cell death [1, 3, 6].