PMID- 16420445 OWN - NLM STAT- MEDLINE DCOM- 20060425 LR - 20170512 IS - 0953-816X (Print) IS - 0953-816X (Linking) VI - 23 IP - 2 DP - 2006 Jan TI - Localization and function of pre- and postsynaptic kainate receptors in the rat globus pallidus. PG - 374-86 AB - Kainate receptors (KARs) are widely expressed the basal ganglia. In this study, we used electron microscopic immunocytochemistry and whole-cell recording techniques to examine the localization and function of KARs in the rat globus pallidus (GP). Dendrites were the most common immunoreactive elements, while terminals forming symmetric or asymmetric synapses and unmyelinated axons comprised most of the presynaptic labeling. To determine whether synaptically released glutamate activates KARs, we recorded excitatory postsynaptic currents (EPSCs) in the GP following single-pulse stimulation of the internal capsule. 4-(8-Methyl-9H-1,3-dioxolo[4,5 h]2,3benzodiazepine-5-yl)-benzenamine hydrochloride (GYKI 52466, 100 microm), an alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist, reduced but did not completely block evoked EPSCs. The remaining EPSC component was mediated through activation of KARs because it was abolished by 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX), an AMPA/KAR antagonist. The rise time (10-90%) and decay time constant (tau) for those EPSCs were longer than those of AMPA-mediated EPSCs recorded before GYKI 52466 application. KAR activation inhibited EPSCs. This inhibition was associated with a significant increase in paired-pulse facilitation ratio, suggesting a presynaptic action of KAR. KAR inhibition of EPSCs was blocked by the G-protein inhibitor, N-ethylmaleimide (NEM), or the protein kinase C (PKC) inhibitor calphostin C. Our results demonstrate that KAR activation has dual effects on glutamatergic transmission in the rat GP: (1) it mediates small-amplitude EPSCs; and (2) it reduces glutamatergic synaptic transmission through a presynaptic G-protein coupled, PKC-dependent, metabotropic mechanism. These findings provide evidence for the multifarious functions of KARs in regulating synaptic transmission, and open up the possibility for the development of pharmacotherapies to reduce the hyperactive subthalamofugal projection in Parkinson's disease. FAU - Jin, Xiao-Tao AU - Jin XT AD - Division of Neuroscience, Yerkes National Primate Research Center and Department of Neurology, Emory University, 954 Gatewood Road NE, Atlanta, GA 30322, USA. FAU - Pare, Jean-Francois AU - Pare JF FAU - Raju, Dinesh V AU - Raju DV FAU - Smith, Yoland AU - Smith Y LA - eng GR - T32 GM008169/GM/NIGMS NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Enzyme Inhibitors) RN - 0 (Excitatory Amino Acid Agonists) RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (Receptors, Kainic Acid) RN - G6D6147J22 (biocytin) RN - K3Z4F929H6 (Lysine) SB - IM MH - Age Factors MH - Animals MH - Animals, Newborn MH - Cell Count MH - Dendrites/drug effects/*physiology MH - Dose-Response Relationship, Drug MH - Drug Interactions MH - Electric Stimulation/methods MH - Enzyme Inhibitors/pharmacology MH - Excitatory Amino Acid Agonists/pharmacology MH - Excitatory Amino Acid Antagonists/pharmacology MH - Excitatory Postsynaptic Potentials/drug effects/physiology/radiation effects MH - Globus Pallidus/*cytology/growth & development MH - In Vitro Techniques MH - Lysine/analogs & derivatives/metabolism MH - Microscopy, Immunoelectron/methods MH - Neurons/*physiology MH - Patch-Clamp Techniques/methods MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Kainic Acid/*metabolism MH - Synapses/*physiology MH - Synaptic Transmission/drug effects/*physiology/radiation effects EDAT- 2006/01/20 09:00 MHDA- 2006/04/28 09:00 CRDT- 2006/01/20 09:00 PHST- 2006/01/20 09:00 [pubmed] PHST- 2006/04/28 09:00 [medline] PHST- 2006/01/20 09:00 [entrez] AID - EJN4574 [pii] AID - 10.1111/j.1460-9568.2005.04574.x [doi] PST - ppublish SO - Eur J Neurosci. 2006 Jan;23(2):374-86. doi: 10.1111/j.1460-9568.2005.04574.x.