A CaV2.1 calcium channel mutation rocker reduces the number of postsynaptic AMPA receptors in parallel fiber-Purkinje cell synapses

Takashi Kodama, Yuko Itsukaichi-Nishida, Yugo Fukazawa, Minoru Wakamori, Mariko Miyata, Elek Molnar, Yasuo Mori, Ryuichi Shigemoto, Keiji Imoto

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

The rocker mice are hereditary ataxic mutants that carry a point mutation in the gene encoding the CaV2.1 (P/Q-type) Ca2+ channel α1 subunit, and show the mildest symptoms among the reported CaV2.1 mutant mice. We studied the basic characteristics of the rocker mutant Ca2+ channel and their impacts on excitatory synaptic transmission in cerebellar Purkinje cells (PCs). In acutely dissociated PC somas, the rocker mutant channel showed a moderate reduction in Ca2+ channel current density, whereas its kinetics and voltage dependency of gating remained nearly normal. Despite the small changes in channel function, synaptic transmission in the parallel fiber (PF)-PC synapses was severely impaired. The climbing fiber inputs onto PCs showed a moderate impairment but could elicit normal complex spikes. Presynaptic function of the PF-PC synapses, however, was unexpectedly almost normal in terms of paired-pulse facilitation, sensitivity to extracellular Ca2+ concentration and glutamate concentration in synaptic clefts. Electron microscopic analyses including freeze-fracture replica labeling revealed that both the number and density of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors substantially decreased without gross structural changes of the PF-PC synapses. We also observed an abnormal arborization of PC dendrites in young adult rocker mice (∼ 1 month old). These lines of evidence suggest that even a moderate dysfunction of CaV2.1 Ca2+ channel can cause substantial changes in postsynaptic molecular composition of the PF-PC synapses and dendritic structure of PCs.

Original languageEnglish
Pages (from-to)2993-3007
Number of pages15
JournalEuropean Journal of Neuroscience
Volume24
Issue number11
DOIs
Publication statusPublished - 2006 Dec
Externally publishedYes

Keywords

  • Cerebellum
  • Dendrite
  • Electrophysiology
  • Freeze-fracture replica-labeling
  • Mouse

ASJC Scopus subject areas

  • Neuroscience(all)

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