Neurosteroid modulation of ionotropic glutamate receptors and excitatory synaptic transmission

Title:

Neurosteroid modulation of ionotropic glutamate receptors and excitatory synaptic transmission

Creator:

Miloslav Sedláček, Miloslav Kořínek, Miloš Petrovič, Cais, O., Adamusová, E., Hana Chodounská, and Ladislav Vyklický

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:65fbf56d-ebdb-4952-b921-11e5c0c2f680
uuid:65fbf56d-ebdb-4952-b921-11e5c0c2f680
issn:0862-8408

Subject:

Fyziologie člověka a srovnávací fyziologie, fyziologie, neurologie, physiology, neurology, N-methyl-D-aspartate receptor, AMPA receptor, glutamate receptor, EPSC, neurosteroid, allosteric modulation, 14, and 612

Type:

article, články, model:article, and TEXT

Format:

print, bez média, and svazek

Description:

Ionotropic glutamate receptors function can be affected by neurosteroids, both positively and negatively. N-methyl-D-aspartate (NMDA) receptor responses to exogenously applied glutamate are potentiated or inhibited (depending on the receptor subunit composition) by pregnenolone sulphate (PS) and inhibited by pregnenolone sulphate (3α5βS). While PS effect is most pronounced when its application precedes that of glutamate, 3α5βS only binds to receptors already activated. Synaptically activated NMDA receptors are inhibited by 3α5βS, though to a lesser extent than those tonically activated by exogenous glutamate. PS, on the other hand, shows virtually no effect on any of the models of synaptically activated NMDA receptors. The site of neurosteroid action at the receptor molecule has not yet been identified, however, the experiments indicate that there are at least two distinct extracellularly located binding sites for PS mediating its potentiating and inhibitory effects respectively. Experiments with chimeric receptors revealed the importance of the extracellular loop connecting the third and the fourth transmembrane domain of the receptor NR2 subunit for the neurosteroid action, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptors are inhibited by both PS and 3α5βS. These neurosteroids also affect AMPA receptors-mediated synaptic transmission, however, in a rather indirect way, through presynaptically located targets of action., M. Sedláček, M. Kořínek, M. Petrovič, O. Cais, E. Adamusová, H. Chodounská, L. Vyklický Jr., and Obsahuje bibliografii a bibliografické odkazy

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Source:

Physiological research | 2008 Volume:57 | Number:Suppl 3

Harvested from:

CDK

Metadata only:

false