bioRxiv / medRxiv
open access
CC0 1.0
WNK-SPAK/OSR1 signaling pathway facilitates ictal activity via reduced neuronal chloride extrusion rate
Seizures upregulate Na+-K+-2Cl- (NKCC1)-mediated Cl- influx and downregulate K+-Cl- (KCC2)-mediated Cl- efflux via the WNK-SPAK/OSR1 kinases, leading to cytoplasmic chloride ([Cl-]i) accumulation, reduced GABAergic inhibition and anticonvulsant failure. Early studies found that inhibiting WNK-kinase
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