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

The sulfonylurea receptor 1-transient receptor potential melastatin 4 channel (SUR1-TRPM4) is a calcium-activated, nonselective monovalent cation channel formed by the association of two protein subunits[1][3]. Under normal conditions, the channel is not expressed; however, it is rapidly upregulated *de novo* in response to various forms of central nervous system injury, including traumatic brain injury, cerebral ischemia, spinal cord injury, and subarachnoid hemorrhage[1]. Upon activation by intracellular calcium, the channel conducts sodium and other cations, causing cell depolarization and promoting secondary injury mechanisms including calcium dysregulation, necrotic cell death, and cerebral edema[1][3]. The channel has emerged as a major therapeutic target, with glibenclamide and other SUR1-TRPM4 inhibitors showing efficacy in reducing hemorrhagic progression and brain swelling in both preclinical models and human clinical trials[5]. Selective targeting of SUR1-TRPM4 over the related SUR1-KIR6.2 channel is important, as the two channels have opposing physiological effects and distinct roles in post-injury pathophysiology[3][5].

Other names

SUR1-regulated nonselective cation-ATP channelSur1-NC(Ca-ATP) channelSUR1-TRPM4 heteromer

Drugs targeting SUR1-TRPM4 work by: - Channel blockade: Inhibiting the nonselective cation conductance of the channel, preventing sodium influx and pathological depolarization[5]. - Prevention of calcium dysregulation: By blocking the channel's depolarizing effect, drugs prevent excessive intracellular calcium accumulation during pathological conditions[1]. - Reduction of cell death: Blocking SUR1-TRPM4 prevents necrotic cell death in the neurovascular unit following CNS injury[3][5].