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PMID: 15175381 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Distinct roles of Galpha(q) and Galpha11 for Purkinje cell signaling and motor behavior.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 24 ·No. 22 ·2004-06-02 ·Pages 5119-30

Hartmann J, Blum R, Kovalchuk Y, Adelsberger H, Kuner R, Durand GM, Miyata M, Kano M, Offermanns S, Konnerth A

Abstract

G-protein-coupled metabotropic glutamate group I receptors (mGluR1s) mediate synaptic transmission and plasticity in Purkinje cells and, therefore, critically determine cerebellar motor control and learning. Purkinje cells express two members of the G-protein G(q) family, namely G(q) and G11. Although in vitro coexpression of mGluR1 with either Galpha11 or Galpha(q) produces equally well functioning signaling cascades, Galpha(q)- and Galpha11-deficient mice exhibit distinct alterations in motor coordination. By using whole-cell recordings and Ca2+ imaging in Purkinje cells, we show that Galpha(q) is required for mGluR-dependent synaptic transmission and for long-term depression (LTD). Galpha11 has no detectable contribution for synaptic transmission but also contributes to LTD. Quantitative single-cell RT-PCR analyses in Purkinje cells demonstrate a more than 10-fold stronger expression of Galpha(q) versus Galpha11. Our findings suggest an expression level-dependent action of Galpha(q) and Galpha11 for Purkinje cell signaling and assign specific roles of these two G(q) isoforms for motor coordination.

MeSH Terms
Animals Behavior, Animal/physiology COS Cells Calcium/metabolism Calcium Signaling/genetics Cerebellum/cytology,metabolism Chlorocebus aethiops Excitatory Postsynaptic Potentials/genetics,physiology Fluorescent Dyes GTP-Binding Protein alpha Subunits, Gq-G11/genetics,metabolism,physiology Long-Term Synaptic Depression/genetics,physiology Mice Mice, Inbred C57BL Mice, Knockout Motor Activity/genetics,physiology Neuronal Plasticity/physiology Patch-Clamp Techniques Protein Subunits/genetics,metabolism,physiology Purkinje Cells/metabolism Receptors, Metabotropic Glutamate/metabolism Signal Transduction/physiology Synaptic Transmission/genetics,physiology
Chemicals
Fluorescent Dyes Protein Subunits Receptors, Metabotropic Glutamate metabotropic glutamate receptor type 1 GTP-Binding Protein alpha Subunits, Gq-G11 Calcium
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Hartmann J
Institut für Physiologie, Ludwig-Maximilians-Universität, 80336 Munich, Germany.
Blum R
Kovalchuk Y
Adelsberger H
Kuner R
Durand G M
Miyata M
Kano M
Offermanns S
Konnerth A
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.4193-03.2004
Published
2004-06-02
Pages
5119-30
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6729195
Subset
IM
External Links
PubMed source DOI: 10.1523/JNEUROSCI.4193-03.2004 PMC Full Text View journal details
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