title: Depolarization-induced slow current in cerebellar Purkinje cells does not require metabotropic glutamate receptor 1.
abstract: Activation of cerebellar Purkinje cells by either brief depolarizing steps or bursts of climbing fiber synaptic activation evokes a slow inward current, which we have previously called depolarization-induced slow current or DISC. DISC is triggered by Ca influx via voltage-sensitive Ca channels and is attenuated by inhibitors of vacuolar ATPase or vesicle fusion. This led us to suggest that DISC required vesicular release of glutamate from the somatodendritic region of Purkinje cells. Furthermore, we found that DISC was attenuated by the mGluR1 antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt), indicating that DISC required autocrine activation of metabotropic glutamate receptor 1 (mGluR1). Here, we have revisited the role of mGluR1 and found that it is, in fact, not required for DISC. CPCCOEt, but not three other specific mGluR1 antagonists (JNJ16259685, alpha-amino-5-carboxy-3-methyl-2-thiopheneacetic acid (3-MATIDA), Bay 36-7620), attenuated DISC, even though all four of these drugs produced near-complete blockade of current evoked by puffs of the exogenous mGluR1/5 agonist DHPG. Cerebellar slices derived from mGluR1 null mice showed substantial DISC that was still attenuated by CPCCOEt. mGluR5 is functionally similar to mGluR1, but is not expressed at high levels in cerebellar Purkinje cells. 2-Methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), an mGluR5 antagonist, did not attenuate DISC, and DISC was still present in Purkinje cells derived from mGluR1/mGluR5 double null mice. Thus, neither mGluR1 nor mGluR5 is required for DISC in cerebellar Purkinje cells.
authors.affiliation: Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Shin
authors.forename: Y S
authors.initials: YS
authors.lastname: Kim
authors.forename: P F
authors.initials: PF
authors.lastname: Worley
authors.forename: D J
authors.initials: DJ
authors.lastname: Linden
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002531:Cerebellum / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques / Q000379:methods; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1