title: A new signalling pathway for parallel fibre presynaptic type 4 metabotropic glutamate receptors (mGluR4) in the rat cerebellar cortex.
abstract: In the rodent cerebellum, pharmacological activation of mGluR4 acutely depresses excitatory synaptic transmission at parallel fibre–Purkinje cell synapses. This depression involves the inhibition of presynaptic calcium (Ca2+) influx that ultimately controls glutamate release. In this study, we investigate the molecular basis of mGluR4-mediated inhibition of presynaptic Ca2+ transients. Our results demonstrate that the mGluR4 effect does not depend on selective inhibition of a specific type of presynaptic voltage-gated Ca2+ channel, but rather involves modulation of all classes of Ca2+ channels present in the presynaptic terminals. In addition, this inhibitory effect does not involve the activation of G protein-activated inwardly rectifying potassium channels, TEA-sensitive potassium channels or two-pore-domain potassium channels. Furthermore, this inhibition does not require pertussis toxin-sensitive G proteins, and is independent of any effect on adenylyl cyclases, protein kinase A, mitogen-activated protein kinases or phosphoinositol-3 kinase activity. Interestingly we found that mGluR4 inhibition of presynaptic Ca2+ influx employs a newly defined signalling pathway, notably that involving the activation of phospholipase C and ultimately protein kinase C.
authors.affiliation: Pharmacology and Biochemistry of the synapse, CNRS UMR 8619, Institut de Biochimie et de Biophysique Moléculaire et Cellulaire, Université Paris-Sud XI, 91405 Orsay Cedex, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Abitbol
authors.forename: Heather
authors.initials: H
authors.lastname: McLean
authors.forename: Thomas
authors.initials: T
authors.lastname: Bessiron
authors.forename: Hervé
authors.initials: H
authors.lastname: Daniel
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology; D002525:Cerebellar Cortex / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D015398:Signal Transduction; D009435:Synaptic Transmission; D010738:Type C Phospholipases / Q000502:physiology
chemical_list: D015220:Calcium Channels; D018094:Receptors, Metabotropic Glutamate; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium; C108823:metabotropic glutamate receptor 4