Aggravation of seizure-like events by hydrogen sulfide: involvement of multiple targets that control neuronal excitability.
OBJECTIVE
Epileptic seizures are well-known neurological complications following stroke, occurring in 3% of patients. However, the intrinsic correlation of seizures with stroke remains largely unknown. Hydrogen sulfide (H2 S) is a gas transmitter that may mediate cerebral ischemic injury. But the role of H2 S in seizures has not been understood yet. We examined the effect of H2 S on seizure-like events (SLEs) and underlying mechanisms.


RESULTS
Pentylenetetrazole (PTZ)- and pilocarpine-induced rat epileptic seizure models were tested. Low-Mg(2+) /high-K(+) - and 4-aminopyridine (4-AP)-induced epileptic seizure models were examined using patch-clamp recordings in brain slices. It was found that NaHS aggravated both PTZ- and pilocarpine-induced SLEs in rats, while both low-Mg(2+) /high-K(+) - and 4-AP-induced SLEs were also exacerbated by NaHS in brain slices, which may be due to its regulation on the voltage-gated sodium channel, N-methyl-D-aspartic acid receptor (NMDAR), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) function. Furthermore, these effects were reversed by blocking voltage-gated sodium channel, NMDAR, and AMPAR.


CONCLUSIONS
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.
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yi
Y
Luo
Peng-Fei
PF
Wu
Jun
J
Zhou
Wen
W
Xiao
Jin-Gang
JG
He
Xin-Lei
XL
Guan
Jie-Ting
JT
Zhang
Zhuang-Li
ZL
Hu
Fang
F
Wang
Jian-Guo
JG
Chen
D015761:4-Aminopyridine; D000818:Animals; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000187:drug effects / Q000503:physiopathology*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008275:Magnesium Deficiency; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010433:Pentylenetetrazole; D010862:Pilocarpine; D011188:Potassium / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D046509:Tissue Culture Techniques; D061567:Voltage-Gated Sodium Channel Blockers / Q000494:pharmacology; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism
D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D061567:Voltage-Gated Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels; D010862:Pilocarpine; D015761:4-Aminopyridine; D011188:Potassium; D010433:Pentylenetetrazole; D006862:Hydrogen Sulfide
Epilepsy; Glutamate receptor; Hydrogen sulfide; Seizure; Voltage-gated sodium channel