Characterization of pre- and post-synaptic metabotropic glutamate receptor-mediated inhibitory responses in substantia nigra dopamine neurons.
Two inhibitory responses mediated by both pre- and post-synaptic metabotropic glutamate receptors (mGluRs) were investigated in dopamine neurons of the substantia nigra using whole-cell patch recordings. (2R,4R)-APDC, a group II mGluR agonist, and L-2-amino-4-phosphonobutyrate (L-AP4), a group III mGluR agonist, reversibly suppressed the amplitude of excitatory postsynaptic currents (EPSCs). However, (S)-3,5-DHPG, a group I mGluR agonist, exhibited less inhibitory action on the EPSCs. LY341495, a highly potent group II mGluR antagonist, antagonized the broad spectrum mGluR agonist, 1S,3R-ACPD-induced suppression of EPSCs. In acutely dissociated dopamine neurons, glutamate (Glu) in the presence of CNQX and AP-5 evoked an outward current accompanied by an increase in K(+) conductance. (S)-3,5-DHPG, but not (2R,4R)-APDC or L-AP4, also induced an outward current. Glu-induced outward current (I(Glu-out)) was partially inhibited by LY367385, a selective mGluR1 antagonist, but not by MPEP, a selective mGluR5 antagonist. Ryanodine and cyclopiazonic acid blocked the I(Glu-out). In the presence of caffeine, Glu failed to induce a current. Charybdotoxin, but not apamin or iberiotoxin, inhibited the I(Glu-out). Taken together, both group II and III mGluRs are mainly involved in the presynaptic inhibition of Glu release to dopamine neurons, while group I mGluRs, including at least mGluR1, participate in the hyperpolarization of dopamine neurons mediated by the opening of charybdotoxin-sensitive Ca(2+)-activated K(+) channels.
Katayama
Jiro
J
Cellular and System Physiology, Graduate School of Medical Science, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582, Japan.
Akaike
Norio
N
Nabekura
Junichi
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D017661:Receptors, Presynaptic; D011188:Potassium; D002118:Calcium; D004298:Dopamine