Phospholipase C-independent group I metabotropic glutamate receptor-mediated inward current in mouse purkinje cells.
The mGluR agonist 1S,3R-ACPD induces a potent excitatory inward current in various central neurons, but the underlying mechanism is not fully understood. Thus, we explored the signal transduction mechanism underlying the 1S,3R-ACPD-induced inward current in mouse cerebellar Purkinje cells. Iontophoretic application of 1S,3R-ACPD produced a group I mGluR antagonist-sensitive inward current. This current closely resembled a slow synaptic inward current evoked by repetitive stimulation of parallel fibers. Although phosphoinositide hydrolysis is shown to be coupled with group I mGluRs, we found that intracellular injections of various PLC inhibitors and an IP3 receptor antagonist heparin only partially inhibited the 1S, 3R-ACPD-induced current. Moreover, intracellular injection of the Ca2+ chelator BAPTA or a selective Na+/Ca2+ exchange inhibitor KB-R7943 affected slightly the inward current. In contrast, infusion of GDPbetaS and GTPgammaS markedly suppressed the 1S,3R-ACPD-induced current. These results suggest that activation of mGluR1 in mouse cerebellar Purkinje cells by 1S,3R-ACPD application or by repetitive stimulation of parallel fibres induces an inward current with a minor contribution from intracellular Ca2+ or Na+/Ca2+ exchange.
Hirono
M
M
Department of Molecular Neurobiology, School of Human Sciences, Waseda University, Tokorozawa, 359, Japan.
Konishi
S
S
Yoshioka
T
T
D000818:Animals; D002118:Calcium / Q000302:isolation & purification; D015220:Calcium Channels / Q000187:drug effects; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004553:Electric Conductivity; D005071:Evoked Potentials; D006493:Heparin / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D053496:Inositol 1,4,5-Trisphosphate Receptors; D051379:Mice; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D015398:Signal Transduction; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors; D013569:Synapses / Q000502:physiology*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D018094:Receptors, Metabotropic Glutamate; D019831:Sodium-Calcium Exchanger; C104077:metabotropic glutamate receptor type 1; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D004533:Egtazic Acid; D006493:Heparin; D010738:Type C Phospholipases; D013890:Thiourea; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium