A selective small-molecule agonist of G protein-gated inwardly-rectifying potassium channels reduces epileptiform activity in a mouse model of tumor associated epilepsy - Part 2: WT Non-Tumor MEA Data

Tumor associated epilepsy is a common and debilitating co-morbidity of
brain tumors, for which inadequate treatments are available. Additionally,
animal models suggest a potential link between seizures and tumor
progression. Our group has previously described a mouse model of diffusely
infiltrating glioma and associated chronic epilepsy. G protein-gated
inwardly rectifying potassium (GIRK) channels are important regulators of
neuronal excitability, but their development as a target of antiseizure
medications has been hampered by cross-reactivity with GIRK channels in
the heart. Recently GiGA1, a novel GIRK agonist that is highly selective
for brain tissue, was developed and shown to have antiseizure properties
in an acute chemoconvulsant model. Here, we test GiGA1 ex vivo in
our established mouse model of tumor associated epilepsy, demonstrating
that a highly selective, small-molecule GIRK agonist can reduce
seizure-like activity in the peritumoral region, where neurons and glioma
cells interact and from which focal seizures arise.