Fig. 11

Model of Sur1-Trpm4 regulation of Ca²⁺ entry, NFAT and Nos2/NOS2 in TLR4-activated microglia. a, b Depiction of NFAT-mediated expression of Nos2/NOS2 in TLR4-activated microglia under normal conditions (a) and following inhibition of Sur1-Trpm4 by glibenclamide (b). Sur1-Trpm4 normally acts, via membrane depolarization, to regulate Ca²⁺ entry via SKF-96395-sensitive channels (e.g., ROCE), leading to activation of calcineurin (CN) and nuclear factor of activated T cells (NFAT), resulting in expression of Nos2/NOS2. When Sur1-Trpm4 is blocked by glibenclamide, excess Ca²⁺ enters the cell, preferentially activating CaMKII, which inhibits CN/NFAT and reduces the expression of Nos2/NOS2