[Synaptic mechanisms of excitatory amino acids and NMDA receptor mediated brain excitability].
L-Glutamate and related excitatory amino acids (EAA) are firmly established as major excitatory synaptic transmitter substances in the vertebrate central nervous system. Questions which have been addressed include: How many receptors are there for the EAAs?; What ion channels and/or 'second-messenger' systems are regulated by these receptors?; What are the roles of EAAs in higher neural functions?; Are they involved in neurological disorders? EAA receptors appear not only to mediate normal synaptic transmission along excitatory pathways but also to participate in the modification of synaptic connections during development. However, overaction of receptors can also mediate neuronal degeneration and even cell death. NMDA receptor antagonists markedly attenuate neuronal necrosis. Therefore, it appears that ischemia- and hypoglycemia-associated brain damage results not from a lack of energy substrates but rather via the mediation of NMDA receptors and 'excitotoxic' mechanisms. The action of ketamine anesthesia is closely associated with a block of the NMDA receptor. Ketamine binds to a site within the lumen of the NMDA-activated channel and can become trapped there when the channel closes. Current evidence indicated that NMDA receptor antagonists will be of value for the treatment of delayed neuronal death. NMDA receptor will lead to understanding the mechanisms underlying learning and memory, the control of neuronal excitability and neuronal death.
Yamamura
T
T
Department of Anesthesiology, Hokkaido University School of Medicine, Sapporo.
Kemmotsu
O
O
D000596:Amino Acids / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000502:physiology*; D006801:Humans; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
D000596:Amino Acids; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate