thiourea and 1-amino-1-3-dicarboxycyclopentane

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.

Topics: Animals; Calcium; Calcium Channels; Cycloleucine; Egtazic Acid; Electric Conductivity; Evoked Potentials; Heparin; Image Processing, Computer-Assisted; Inositol 1,4,5-Trisphosphate Receptors; Mice; Patch-Clamp Techniques; Purkinje Cells; Receptors, Cytoplasmic and Nuclear; Receptors, Metabotropic Glutamate; Signal Transduction; Sodium-Calcium Exchanger; Synapses; Thiourea; Type C Phospholipases