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

The SUR1-TRPM4 channel complex is a heteromeric ion channel composed of the regulatory sulfonylurea receptor 1 (SUR1) and the pore-forming transient receptor potential melastatin 4 (TRPM4) subunit (Simard et al., 2007, Nature Medicine). Under physiological conditions, this complex is minimally expressed in the central nervous system; however, it is rapidly upregulated de novo in neurons, astrocytes, and capillary endothelium following acute injuries such as ischemic stroke, traumatic brain injury, and spinal cord injury (Simard et al., 2006, Journal of Neuroscience). Activation of the channel occurs in response to depleted intracellular ATP and elevated calcium levels, leading to a non-selective influx of monovalent cations that drives cytotoxic edema and oncotic cell death (Gerzanich et al., 2009, Journal of Cerebral Blood Flow & Metabolism). This process contributes significantly to blood-brain barrier breakdown and secondary brain swelling. Targeting the SUR1-TRPM4 complex with inhibitors like glibenclamide (BIIB093) aims to reduce edema and improve neurological recovery by blocking this pathological ion flux (Sheth et al., 2016, Lancet Neurology). This therapeutic approach is currently being evaluated in clinical trials for large hemispheric infarction and other forms of acute brain injury.

Other names

SUR1-regulated NCCa-ATP channelABCC8-TRPM4 complexSulfonylurea receptor 1-TRPM4 channelNCCa-ATP channel

Inhibition of the SUR1-TRPM4 complex prevents the pathological influx of monovalent cations, thereby mitigating cytotoxic edema, oncotic cell death, and blood-brain barrier disruption in acute central nervous system injuries (Simard et al., 2012, Pharmaceuticals).