Hydrogen sulfide is produced in response to neuronal excitation.
Although hydrogen sulfide (H2S) is generally thought of in terms of a poisonous gas, it is endogenously produced in the brain. Physiological concentrations of H2S selectively enhance NMDA receptor-mediated responses and alter the induction of hippocampal long-term potentiation (LTP). Here we use cystathionine beta-synthase (CBS) knock-out mice to clearly show that CBS produces endogenous H2S in the brain and that H2S production is greatly enhanced by the excitatory neurotransmitter l-glutamate, as well as by electrical stimulation. This increased CBS activity is regulated by a pathway involving Ca2+/calmodulin. In addition, LTP is altered in CBS knock-out mice. These observations suggest that H2S is produced by CBS in response to neuronal excitation and that it may regulate some aspects of synaptic activity.
Eto
Ko
K
National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8551, Japan.
Ogasawara
Miki
M
Umemura
Ken
K
Nagai
Yasuo
Y
Kimura
Hideo
H
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001923:Brain Chemistry; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000737:chemistry / Q000172:deficiency / Q000235:genetics; D003545:Cysteine / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000032:analysis / Q000378:metabolism*; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D014162:Transfection
D002147:Calmodulin; D004791:Enzyme Inhibitors; D007476:Ionophores; D018698:Glutamic Acid; D003541:Cystathionine beta-Synthase; D003545:Cysteine; D002118:Calcium; D006862:Hydrogen Sulfide