The SUR1-regulated NC_Ca-ATP channel and the SUR1-regulated K_ATP channel have similar pharmacological profiles but very different channel properties. Like K_ATP, NC_Ca-ATP is inhibited by intracellular ATP (A) and is blocked by glibenclamide in a pH-dependent manner (D,E). However, unlike K_ATP, NC_Ca-ATP requires intracellular Ca²⁺ (B) and it conducts all monovalent cations (C). Panels A, B, D from Simard et al., 2006 [9], with permission; panel C from Chen and Simard, 2001 [24], with permission; panel E, from Chen et al., 2003 [8], with permission (○), and unpublished observations (●) (J. M. Simard and M. Chen).

SUR1 is upregulated in human brain tissues with injury. Freshly isolated human gliotic capsule shows widespread SUR1 expression in astrocytes co-labeled for GFAP (A). Freshly isolated tissue adjacent to intracerebral hemorrhage (*) shows widespread SUR1 protein (B, left panel) and mRNA (C, left panel) in large neuron-like cells and microvessels; post-mortem human brain tissue (B, right panel) and tissue adjacent to intracerebral hemorrhage labeled with sense probe (C, right panel) showed minimal signal; methods for immunohistochemistry and in situ hybridization as in Simard et al., 2006 [9].

Schematic diagram illustrating various types of edema progressing to hemorrhagic conversion in the CNS. Normally, Na⁺ concentrations in serum and in extracellular space are the same, and much higher than inside the neuron. Cytotoxic edema of neurons is due to entry of Na⁺ into ischemic neurons via pathways such as SUR1-regulated NC_Ca-ATP channels, depleting extracellular Na⁺ and thereby setting up a concentration gradient between intravascular and extracellular compartments. Ionic edema results from cytotoxic edema of endothelial cells, due to expression of cation channels on both the luminal and abluminal side, allowing Na⁺ from the intravascular compartment to traverse the capillary wall and replenish Na⁺ in the extracellular space. Vasogenic edema results from degradation of tight junctions between endothelial cells, transforming capillaries into “fenestrated” capillaries that allow extravasation (outward filtration) of proteinatious fluid. Oncotic death of neuron is the ultimate consequence of cytotoxic edema. Oncotic death of endothelial cells results in complete loss of capillary integrity and in extravasation of blood, i.e., hemorrhagic conversion. From Simard et al. [2], with permission.