Aggravation of Seizure‐like Events by Hydrogen Sulfide: Involvement of Multiple Targets that Control Neuronal Excitability

Abstract

These results suggest a pathological role of increased H2 S level in SLEs in vivo and in vitro. Enzymes that control H2 S biosynthesis could be interesting targets for antiepileptic strategies in poststroke epilepsy treatment.

Hydrogen sulfide inhibits Kir2 and Kir3 channels by decreasing sensitivity to the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2)

“…H 2 S mediates ischemic damage pursuant to stroke in neuronal tissue (15), whereas it serves as a powerful cardioprotective agent upon comparable conditions. One categorical correlation that emerged in the studies highlighting this 'dual physiological effect' by the gaseous mediator is that while H 2 S depolarizes cerebral components (8)(9)(10)(11)(12), it hyperpolarizes cardiomyocytes (13,14). In other words, H 2 S increases the excitability of cerebral tissue, worsening seizure-like symptoms and rendering neurons more susceptible to ischemic insult (12,15).…”

“…One categorical correlation that emerged in the studies highlighting this 'dual physiological effect' by the gaseous mediator is that while H 2 S depolarizes cerebral components (8)(9)(10)(11)(12), it hyperpolarizes cardiomyocytes (13,14). In other words, H 2 S increases the excitability of cerebral tissue, worsening seizure-like symptoms and rendering neurons more susceptible to ischemic insult (12,15). In contrast, H 2 S depresses the excitability of the heart, in which H 2 S is cardioprotective in ischemia and reperfusion (I/R) injury models when administered either through a pre-I/R (16,18,19) or post-I/R (20) treatment regime.…”

“…Thus, subsequent efforts have been made to identify key ion channels that contribute to the depolarizing effect of H 2 S on neuronal cells. To date, the identity of H 2 S-sensitive ion channels in specific neuronal tissues has remained elusive (8)(9)(10)(11)(12). Relying on ion channel blockers with limited specificity has made it difficult to reliably correlate the effect of H 2 S on observed depolarizations in neurons to specific ion channels.…”

“…Collectively, H 2 S has been shown to play a role in diverse physiological processes, such as cellular necrosis, apoptosis, oxidative stress, or inflammation (7). One theme emerging from these studies is that H 2 S increases the excitability of neuronal compartments (8-12), whereas it depresses excitability of cardiac tissues (13,14), correlating to neurotoxic (12,15) and cardioprotective (16)(17)(18)(19)(20) effects, respectively. Therefore, exactly how H 2 S is affecting differentially ion channels expressed in cells that rapidly control membrane excitability has become a central question.…”

Hydrogen Sulfide Promotes Learning and Memory and Suppresses Proinflammatory Cytokines in Repetitive Febrile Seizures

“…Previous studies have also shown that H 2 S can increase neuronal excitability in rat trigedeminal ganglion neurons [27] and rat epileptic seizure models [28] . In addition, an increase in the plasma level of H 2 S was found in a febrile seizure rat model [29] .…”