Kainate acts at presynaptic receptors to increase GABA release from hypothalamic neurons.
Recent reports suggest that kainate acting at presynaptic receptors reduces the release of the inhibitory transmitter GABA from hippocampal neurons. In contrast, in the hypothalamus in the presence of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor antagonists [1-(4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466) and D,L-2-amino-5-phosphonopentanoic acid (AP5)], kainate increased GABA release. In the presence of tetrodotoxin, the frequency, but not the amplitude, of GABA-mediated miniature inhibitory postsynaptic currents (IPSCs) was enhanced by kainate, consistent with a presynaptic site of action. Postsynaptic activation of kainate receptors on cell bodies/dendrites was also found. In contrast to the hippocampus where kainate increases excitability by reducing GABA release, in the hypothalamus where a much higher number of GABAergic cells exist, kainate-mediated activation of transmitter release from inhibitory neurons may reduce the level of neuronal activity in the postsynaptic cell.
Liu
Q S
QS
Department of Neurosurgery, Yale University Medical School, New Haven, Connecticut 06520, USA.
Patrylo
P R
PR
Gao
X B
XB
van den Pol
A N
AN
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001569:Benzodiazepines; D002478:Cells, Cultured; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017661:Receptors, Presynaptic / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D018691:Excitatory Amino Acid Antagonists; D017661:Receptors, Presynaptic; C061950:GYKI 52466; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid; D007608:Kainic Acid