Preferential block of desensitizing AMPA receptor in hippocampal neurons by gamma-D-glutamylaminomethylsulfonic acid.
The (RS)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolopropionic acid (AMPA)/kainate receptor-channel complex mediates fast components of excitatory synaptic currents in the central nervous system. Distinguishing between these components is a difficult pharmacological task. As was recently reported, gamma-D-glutamylaminomethylsulfonic acid (GAMS) may be a selective kainate receptor antagonist. We have tested this possibility in experiments which were carried out on acutely isolated rat hippocampal neurons. It appeared that 1 mM GAMS first blocked 83 +/- 1% of the fast desensitizing 128 microM AMPA-gated current, but only 38 +/- 6% of the non-desensitizing current component and reached, at higher GAMS concentrations, a plateau at about 50% of the control steady state current level. In contrast to the blocking action of GAMS on AMPA-gated currents, 4-fold higher concentrations of GAMS were needed to block currents elicited by 256 microM kainate application. It is suggested that several subunit compositions of the AMPA-gated receptor could coexist on a single hippocampal cell. Furthermore, GAMS has a certain preference for subunit assemblies which could mediate fast desensitizing and, a portion of, the non-desensitizing current component.
Wilsch
V W
VW
Department of Neurophysiology, Federal Institute for Neurobiology, Magdeburg, Germany.
Pidoplichko
V I
VI
Reymann
K G
KG
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005973:Glutamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007473:Ion Channels; D018091:Receptors, AMPA; D005973:Glutamine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C042626:gamma-glutamylaminomethylsulfonic acid; D007608:Kainic Acid