@misc{oai:ir.soken.ac.jp:00001117, author = {松下, かおり and マツシタ, カオリ and MATSUSHITA, Kaori}, month = {2016-02-17, 2016-02-17}, note = {Recent genetic and molecular biological analyses have revealed many forms of inherited channelopathies, and single gene mutations is directly responsible for the neurological phenotypes. Homozygous ataxic mice, tottering (tg) and rolling Nagoya (tg^rol), have mutations in the P/Q-type Ca²⁺ channel α_1A subunit gene. The location of the mutations and the neurological phenotypes are known, but the mechanisms how the mutations cause the symptoms and how the different mutations lead to various onset and severity have remained unsolved. Here she compared fundamental properties of excitatory synaptic transmission in the cerebellum and its sensitivity to subtype-specific Ca²⁺ channel blockers among wild-type control, tg, and tg^rol mice. The amplitude of excitatory posysynaptic current (EPSC) of the parallel fiber-Purkinje cell (PF-PC) synapses was considerably reduced in ataxic tg^rol. Whereas the PF-PC EPSC was only mildly decreased in non-alaxic tg mice, the PF-PC EPSC was drastically diminished in ataxic tg mice of P28-35. In contrast, the EPSC amplitude of the climbing fiber-Purkinje cell (CF-PC) synapses was preserved in tg, and it was even increased in tg^rol. CF-PC EPSC was more dependent on the N- and R-types in mutant mice, suggesting that such compensatory mechanisms maintain the CF-PC synaptic transmission virtually intact. The results indicate that the impairment of the PF-PC synaptic transmission well correlates with manifestation of ataxia, and that different mutations of the P/Q- type Ca²⁺ channel not only cause the primary effect of various severity but also lead to diverse secondary effects, which include up-regulation of other Ca²⁺ channel subtypes and enhancement of sensitivity of postsynaptic glutamate receptors., 総研大甲第561号}, title = {Electrophysiological Studies on Cerebellar Synaptic Transmission in P/Q-type Ca2+ Channel Mutant Mice}, year = {} }