Biomedical subjects

Yoshihiro Matsuda

Publications and source records attributed to Yoshihiro Matsuda.

5 recordsLinked to original sources

PubMed2006

Properties of human Cav2.1 channel with a spinocerebellar ataxia type 6 mutation expressed in Purkinje cells.

Spinocerebellar ataxia type 6 (SCA6) is caused by polyglutamine expansion in P/Q-type Ca2+ channels (Ca(v)2.1) and is characterized by predominant degeneration of cerebellar Purkinje cells. To characterize the Ca(v)2.1 channel with an SCA6 mutation in cerebellar Purkinje cells, we have generated knock-in mouse models that express human Ca(v)2.1 with 28 polyglutamine repeats (disease range) and with 13 polyglutamine repeats (normal range). Patch-clamp recordings of the Purkinje cells from homozygous control or SCA6 knock-in mice revealed a non-inactivating current that is highly sensitive to a spider toxin omega-Agatoxin IVA, indicating that the human Ca(v)2.1 expressed in Purkinje cells exhibits typical P-type properties in contrast to the previous data showing Q-type properties, when it was expressed in cultured cell lines. Furthermore, the voltage dependence of activation and inactivation and current density were not different between SCA6 and control, though these properties were altered in previous reports using non-neuronal cells as expression systems. Therefore, our results do not support the notion that the alteration of the channel properties may underlie the pathogenic mechanism of SCA6.

Age Factors↗

PubMed2005

The regulatory networks of gene expression during the sexual differentiation of Chlamydomonas reinhardtii, as analyzed by mutants for gametogenesis.

Cells of Chlamydomonas reinhardtii differentiate into gametes under conditions of nitrogen (N) starvation, expressing the genes for the N-adaptation program and the gamete program. To investigate the regulatory networks of transcription among the N-starvation-inducible genes, we examined the gene expression in dif mutants, affecting gametic differentiation. In a conditional mutant, dif2, the cells remained 'vegetative' at the restrictive temperature, and the induction of 20 out of 21 genes related to the two programs was impaired. They were expressed soon after transfer of the cells to the permissive temperature, in parallel with the acquisition of mating ability. In an unconditional mutant, dif3, the cells could not differentiate into gametes at all, but the induction of only four genes (FUS1, NSG3, NSG6 and NSG7) related to the gamete program was impaired. The results suggest that Dif3 regulates putative N-starvation signal transduction pathways downstream of a master regulator, Dif2. We also examined a light-dependent laboratory strain that was unable to become gametes in the dark. The 'pre-gametes' placed in the dark, however, could induce normally all of the 21 genes, suggesting that light is required for the gametic differentiation at the translational and/or post-translational levels.

Adaptation, Physiological↗

PubMed2002

Genealogical relationships among laboratory strains of Chlamydomonas reinhardtii as inferred from matrix metalloprotease genes.

Almost all research on Chlamydomonas reinhardtii has utilized wild-type strains of three principal stock lines (Sager, Cambridge, Ebersold-Levine), which traditionally has been assumed to be descendants of a single zygote isolated by Smith. We previously noticed that there are several sequence differences in a single-copy gene of gametolysin, mmp1, between the mt+ and mt- strains employed. To further examine the polymorphisms among the three lines, we obtained 18 representative strains of all three descendant lines of Smith's isolate, nine strains recently isolated from the wild and one strain (CC-1373 mt+) of C. smithii, a strain from Smith's collection interfertile with these C. reinhardtii strains; and we compared the mmp1-3'UTR by RFLP and sequencing analyses. Sequence divergences were found between the mt+ and mt- strains of both the Sager and Cambridge lines, but not between the two mating-type strains of the Ebersold-Levine line. We also examined the polymorphisms, using the 3'UTRs of two other mmp genes and the introns of ypt4 and fus1. Based on the results, we conclude that it is genetically impossible for all the current C. reinhardtii lines to be the immediate descendants of a single zygote.

3' Untranslated Regions↗

PubMed2002

Effects of ablation of N- and R-type Ca(2+) channels on pain transmission.

Recently several mutant mouse lines lacking neuronal voltage-dependent Ca(2+) channels (VDCCs) have been established by the use of gene targeting in embryonic stem cells. Pain-related behaviors in Ca(v)2.2 (alpha(1B)) and Ca(v)2.3 (alpha(1E)) knockout mice were studied to gain further insight into the mechanism of pain transmission, where VDCCs are thought to play important roles. We review here the data from these recent studies. Ca(v)2.3-/- mice showed normal responses to acute painful stimuli, and reduced responses to the somatic inflammatory pain stimuli. Ca(v)2.3+/- mice exhibited reduced symptoms of visceral inflammatory pain. Ca(v)2.3-/- mice showed abnormal behavior related to the descending antinociceptive mechanism activated by the intraperitoneal injection of acetic acid. Ca(v)2.2-/- mice showed variable acute nociceptive responses depending on the mutant lines. However, all the lines of Ca(v)2.2-/- mice exhibited reduced responses in the phase 2 of the formalin test, suggesting a suppression of inflammatory pain. Furthermore Ca(v)2.2-/- mice showed markedly reduced neuropathic pain symptoms after spinal nerve ligation. Impaired antinociception, similar to that seen in the Ca(v)2.3-/- mice, was also observed in the Ca(v)2.2-/- mice. Therefore, it is suggested that these mutant mice could provide novel models to delineate the nociceptive and antinociceptive mechanisms.

Acetic Acid↗

PubMed2002

[Structure and function of T-type calcium channels].

Molecular structure of the T-type Ca(2+) channel was first clarified by the cloning of Ca(V)3.1 (alpha(1G)) as an authentic component of the T-type channel. Since then, much progress has been made in understanding functions of the T-type Ca(2+) channels, because it has become possible to study structure-function relationship for the T-type channel using mutagenesis techniques and to examine abnormal phenotypes of T-type channel knock-out mice. Here we will review briefly the recent progress in studies on structure and function of T-type Ca(2+) channels.

English Abstract↗