Ionotropic glutamate receptor biology: effect on synaptic connectivity and function in neurological disease.
Glutamate receptor signaling is essential to normal synaptic function in the central nervous system. The major ionotropic glutamate receptors (AMPA, Kainic, and NMDA) have different synaptic functions depending upon cellular and subcellular localization, subunit composition, and second messenger systems linked to the receptors. In this review, we examine major advances in glutamate receptor biology whose physiology plays a central role in neurologic disease such as epilepsy and stroke. A key feature of glutamate receptor activation in neurologic disease is the downstream effects on cell survival, genetic expression of axon guidance cues, synaptic connectivity/formation of networks, and neuronal excitability. Identification of therapeutic pharmacologic targets and development of antagonists specific to the disease process remain central themes in epilepsy and stroke research.
Barnes
G N
GN
Developmental Neurobiology Laboratory, Department of Neurology, L441, Wing D, KY Clinic, 704 South Limestone, Lexington, KY 40536, USA. Gnbarn2@uky.edu
Slevin
J T
JT
D018846:Excitatory Amino Acids / Q000266:history / Q000502:physiology; D006624:Hippocampus / Q000033:anatomy & histology / Q000166:cytology / Q000378:metabolism; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D009422:Nervous System Diseases / Q000209:etiology*; D018091:Receptors, AMPA / Q000378:metabolism / Q000502:physiology; D017470:Receptors, Glutamate / Q000378:metabolism / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000378:metabolism / Q000502:physiology; D013569:Synapses / Q000378:metabolism / Q000502:physiology*
D018846:Excitatory Amino Acids; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors