Biomedical subjects

Shin-Ya Saito

Publications and source records attributed to Shin-Ya Saito.

4 recordsLinked to original sources

PubMed2006

Functional uncoupling between Ca2+ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins.

Junctional membrane complexes (JMCs) composed of the plasma membrane and endoplasmic/sarcoplasmic reticulum seem to be a structural platform for channel crosstalk. Junctophilins (JPs) contribute to JMC formation by spanning the sarcoplasmic reticulum membrane and binding with the plasma membrane in muscle cells. In this article, we report that mutant JP double-knockout (JP-DKO) mice lacking neural JP subtypes exhibited an irregular hindlimb reflex and impaired memory. Electrophysiological experiments indicated that the activation of small-conductance Ca(2+)-activated K(+) channels responsible for afterhyperpolarization in hippocampal neurons requires endoplasmic reticulum Ca(2+) release through ryanodine receptors, triggered by NMDA receptor-mediated Ca(2+) influx. We propose that in JP-DKO neurons lacking afterhyperpolarization, the functional communications between NMDA receptors, ryanodine receptors, and small-conductance Ca(2+)-activated K(+) channels are disconnected because of JMC disassembly. Moreover, JP-DKO neurons showed an impaired long-term potentiation and hyperactivation of Ca(2+)/calmodulin-dependent protein kinase II. Therefore, JPs seem to have an essential role in neural excitability fundamental to plasticity and integrated functions.

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PubMed2006

DNER as key molecule for cerebellar maturation.

Notch signaling plays an important role in the process of cell-fate assignation during nervous system development. DNER is a neuron-specific transmembrane protein carrying extracellular EGF-like repeats and is expressed in somatodendritic regions. In vitro studies demonstrated that DNER mediates Notch signaling by cell-cell interaction. In the cerebellum, DNER is abundantly expressed in Purkinje cells and moderately in granule cells. DNER-knockout mice showed motor discoordination. The mutant cerebellum showed morphological impairments of Bergmann glia and multiple innervation between climbing fibers and Purkinje cells. Moreover, glutamate clearance at the synapses between parallel fibers and Purkinje cells was significantly weakened, and the expression of GLAST, a glutamate transporter in Bergmann glia, was reduced in the mutant cerebellum. Therefore, DNER contributes to the morphological and functional maturation of Bergmann glia via the Notch signaling pathway, and is essential for precise cerebellar development.

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PubMed2004

Evidence for the involvement of protein kinase C in acidic pH-induced contraction in spontaneously hypertensive rat aorta.

This study was performed to test the hypothesis that activation of protein kinase C (PKC) is a mechanism underlying the acidic pH-induced contraction (APIC) in spontaneously hypertensive rat (SHR) aorta. Changing pH of the bathing solution from 7.4 to 6.5 induced a marked contraction of SHR aorta. PKC inhibitors, GF109203X and calphostin C markedly inhibited the APIC selectively, without having a marked effect on the KCl-induced contraction. Inhibitors of mitogen-activated protein kinase kinase, U0126 and PD98059 mildly but significantly attenuated the APIC. However, at the similar concentrations both U0126 and PD98059 inhibited the KCl-induced contraction in a manner similar to that observed in APIC. D-609, an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC) markedly inhibited the APIC and the extent of inhibition by this compound was similar to that shown by PKC inhibitors. Whereas, U-73122 and propranolol, inhibitors of phosphatidylinositol-specific PLC and phosphatidate phosphohydrolase, respectively, had no affect on the APIC. A tyrosine kinase inhibitor, tyrphostin 23 and GF109203X inhibited the APIC in an additive manner, and together they abolished the contractile response. From all these results, it is suggested that a significant component of the contraction observed in response to acidosis in SHR aorta is dependent upon the activation of PKC that seems to be the downstream event of the activation of PC-PLC. Furthermore, PKC- and tyrosine kinase-dependent pathways underlying the APIC are independent of each other.

Animals↗

PubMed2004

The combination of rat mast cell and rabbit aortic smooth muscle is the simple bioassay for the screening of anti-allergic ingredient from methanolic extract of Corydalis tuber.

We have assessed the release of histamine from mast cells by smooth muscle contraction. 0.3 microg/ml compound 48/80 showed no effect on concentration-response relationship of histamine in rabbit aorta. Compound 48/80 induced release of histamine from rat mast cells. When aorta was stimulated by compound 48/80 in the presence of mast cells, contraction was evoked in concentration-dependent manner. This mast cell-dependent contraction was completely blocked by H1 receptor antagonist, 1 microM diphenhydramine. When mast cells was treated with compound 48/80 inhibitor benzalkonium chloride, mast cell-dependent contraction was inhibited, although benzalkonium chloride itself showed no effect on concentration-response relationship of histamine in rabbit aorta. At high concentration of 10 microg/ml, benzalkonium chloride itself evoked histamine release from mast cells and indeed inhibitory effect of 10 microg/ml benzalkonium chloride on mast cell-dependent contraction was lower than that of 3 microg/ml. We have applied this bioassay to search anti-allergic ingredient from a total methanolic extract of Corydalis tuber (Corydalis turtschaninovii BESSER forma yanhusuo Y. H. CHOU et C. C. HSU). Successively, we have isolated five fractions. The fractions I-IV are identified to be corybulbine (1), tetrahydropalmatine (2), corydaline (3) and yuanhunine (4), respectively. Main component of fraction V is the mixture of 3 and canadine (5). Fractions II and V significantly inhibited mast cell-dependent contraction in rabbit aorta as well as inhibited histamine release from rat mast cells. Furthermore, fractions I, III and V inhibited histamine-induced contraction in rabbit aorta at non-competitive manner. From these results, combination of rat mast cells and rabbit aorta is good bioassay to search the anti-allergic ingredient, and we have obtained effective fractions from Corydalis tuber using this assay.

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