egl‑4 modulates electroconvulsive seizure duration in C. elegans

Increased neuronal excitability causes seizures with debilitating symptoms. Effective and noninvasive treatments are limited
for easing symptoms, partially due to the complexity of the disorder and lack of knowledge of specific molecular faults. An
unexplored, novel target for seizure therapeutics is the cGMP/protein kinase G (PKG) pathway, which targets downstream
K+
channels, a mechanism similar to Retigabine, a recently FDA-approved antiepileptic drug. Our results demonstrate that
increased PKG activity decreased seizure duration in C. elegans utilizing a recently developed electroconvulsive seizure
assay. While the fly is a well-established seizure model, C. elegans are an ideal yet unexploited model which easily uptakes
drugs and can be utilized for high-throughput screens. In this study, we show that treating the worms with either a potassium
channel opener, Retigabine or published pharmaceuticals that increase PKG activity, significantly reduces seizure recovery
times. Our results suggest that PKG signaling modulates downstream K+
channel conductance to control seizure recovery
time in C. elegans. Hence, we provide powerful evidence, suggesting that pharmacological manipulation of the PKG signaling
cascade may control seizure duration across phyla.