Differential pharmacological properties of GABAA receptors in axon terminals and soma of dentate gyrus granule cells.
Although it has been well established that GABA(A) receptors are molecular targets of a variety of allosteric modulators, such as benzodiazepines, the pharmacological properties of presynaptic GABA(A) receptors are poorly understood. In this study, the effects of diazepam and Zn(2+) on presynaptic GABA(A) receptors have been investigated by measuring the GABA(A) receptor-mediated facilitation of spontaneous glutamate release in mechanically dissociated rat CA3 pyramidal neurons. Diazepam significantly enhanced the muscimol-induced facilitation (particularly at submicromolar concentrations) of spontaneous glutamate release and shifted the concentration-response relationship for muscimol toward the left, whereas Zn(2+) (<OR= 100 muM) had little effect on the muscimol-induced facilitation of spontaneous glutamate release. In contrast, Zn(2+) significantly suppressed the muscimol-induced currents mediated by GABA(A) receptors expressed on dentate gyrus granule cells, which are parent neurons of mossy fibers, whereas the effect of diazepam on GABA(A) receptors expressed on dentate gyrus granule cells was lesser than that on presynaptic GABA(A) receptors. The results suggest that the pharmacological properties of GABA(A) receptors differ considerably between presynaptic (axon terminals) and somatic regions in the same granule cell and that presynaptic GABA(A) receptors should be considered as one of the important pharmacological targets of many drugs affecting GABA(A) receptors.
Han
Jin-Wuk
JW
Department of Oral Surgery, School of Dentistry, Kyungpook National University, Daegu, Korea.
Nakamura
Michiko
M
Choi
In-Sun
IS
Cho
Jin-Hwa
JH
Park
Hye-Mi
HM
Lee
Maan-Gee
MG
Choi
Byung-Ju
BJ
Jang
Hyun-Jung
HJ
Jang
Il-Sung
IS
D000465:Algorithms; D000818:Animals; D003627:Data Interpretation, Statistical; D018891:Dentate Gyrus / Q000166:cytology* / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018755:GABA Agonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D015032:Zinc / Q000494:pharmacology
D018755:GABA Agonists; D018757:GABA Modulators; D011963:Receptors, GABA-A; D009118:Muscimol; D015032:Zinc; D003975:Diazepam