Depolarization-induced slow current in cerebellar Purkinje cells does not require metabotropic glutamate receptor 1

J. H. Shin, Yu Shin Kim, P. F. Worley, D. J. Linden

Research output: Contribution to journalArticle

5 Citations (Scopus)

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, α-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.

Original languageEnglish (US)
Pages (from-to)688-693
Number of pages6
JournalNeuroscience
Volume162
Issue number3
DOIs
StatePublished - Sep 1 2009
Externally publishedYes

Fingerprint

Purkinje Cells
Excitatory Amino Acid Antagonists
Esters
Vacuolar Proton-Translocating ATPases
metabotropic glutamate receptor type 1
Glutamic Acid

Keywords

  • autocrine
  • CPCCOEt
  • DHPG
  • mGluR5

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Depolarization-induced slow current in cerebellar Purkinje cells does not require metabotropic glutamate receptor 1. / Shin, J. H.; Kim, Yu Shin; Worley, P. F.; Linden, D. J.

In: Neuroscience, Vol. 162, No. 3, 01.09.2009, p. 688-693.

Research output: Contribution to journalArticle

Shin, J. H. ; Kim, Yu Shin ; Worley, P. F. ; Linden, D. J. / Depolarization-induced slow current in cerebellar Purkinje cells does not require metabotropic glutamate receptor 1. In: Neuroscience. 2009 ; Vol. 162, No. 3. pp. 688-693.
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