Allosteric potentiation by diazoxide of AMPA receptor currents and synaptic potentials
Diazoxide (100–560 μM) reversibly increased the amplitude and duration of excitatory post-synaptic field potentials recorded in the dentate gyrus of hippocampal slices following stimulation of the perforant pathway. In rat cortex mRNA-injected Xenopus oocytes diazoxide (1–1000 μM) alone had little e...
Saved in:
Published in | European journal of pharmacology Vol. 247; no. 3; pp. 257 - 265 |
---|---|
Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Amsterdam
Elsevier B.V
15.11.1993
Elsevier |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Diazoxide (100–560 μM) reversibly increased the amplitude and duration of excitatory post-synaptic field potentials recorded in the dentate gyrus of hippocampal slices following stimulation of the perforant pathway. In rat cortex mRNA-injected
Xenopus oocytes diazoxide (1–1000 μM) alone had little effect on membrane current, but rapidly and reversibly increased (up to 5-fold) current responses to (
R,
S)-α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA, 30 μM),
l-glutamate (100 μM), quisqualate (3 μM), kainate (100 μM) and domoate (3 μM), an effect that was neither mimicked by other activators of ATP-sensitive potassium channels nor blocked by glibenclamide. Diazoxide increased current amplitudes for all concentrations of the ‘inactivating’ ligands, AMPA,
l-glutamate and quisqualate but had little effect on their EC
50 values. In contrast, diazoxide increased the apparent potency of the ‘non-inactivating’ ligands, kainate and domoate, but increased the efficacy of saturating concentrations by only 10–20%. Diazoxide did not modify the competitive inhibition of AMPA and kainate currents by 6-nitro-7-sulfamoylbenzo[f]quinoxaline-2,3-dione (NBQX) and thus does not compete for the agonist site as do AMPA and kainate. Similarly, diazoxide neither inhibited the binding of [
3H]AMPA or [
3H]kainate to rat cortical membranes in competition experiments nor consistenty modified the apparent [
3H]AMPA affinity (
K
d) or receptor density (
B
max) in saturation experiments. These data suggest that diazoxide acts at an allosteric site on the AMPA receptor/channel to potentiate activation in a manner dependent upon the properties of the excitatory agonist. |
---|---|
Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0922-4106 0014-2999 |
DOI: | 10.1016/0922-4106(93)90193-D |