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

The Sulfonylurea receptor 1-Transient receptor potential melastatin 4 (SUR1-TRPM4) channel is a heteromeric, non-selective cation channel that is de novo expressed in the central nervous system following acute injury (Simard et al., 2006). It consists of the regulatory SUR1 subunit, an ATP-binding cassette protein, and the pore-forming TRPM4 subunit, a member of the transient receptor potential family (Woo et al., 2013). Under normal conditions, this channel is not present in brain cells, but it is rapidly upregulated in neurons, astrocytes, and vascular endothelium in response to ischemia, hypoxia, or trauma (Kurland et al., 2013). Once expressed and activated by depleted intracellular ATP, the channel allows for a massive influx of sodium ions, which drives water into the cells, leading to cytotoxic edema and oncotic cell death (Simard et al., 2007). This process is a major contributor to secondary brain damage, including midline shift and blood-brain barrier breakdown in conditions like ischemic stroke and traumatic brain injury. The channel is the primary target of the sulfonylurea drug glibenclamide, which inhibits the channel's activity by binding to the SUR1 subunit (Sheth et al., 2014). Clinical development of intravenous glibenclamide (BIIB093) has focused on reducing cerebral edema and improving functional outcomes in patients with large hemispheric infarctions.

Other names

SUR1-regulated NCCa-ATP channelNC(Ca-ATP) channelSUR1-TRPM4 complexSulfonylurea receptor 1-Transient receptor potential melastatin 4 complex

Inhibition of the non-selective cation current by binding to the SUR1 regulatory subunit, preventing pore opening and subsequent sodium-driven water influx.