EXPRESSION OF IONIC CHANNELS DURING CARDIOVASCULAR DISEASE
| Project/Area Number |
10044313
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | NAGOYA CITY UNIVERSITY |
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Principal Investigator |
IMAIZUMI Yuji NAGOYA CITY UNIVERSITY, PHARMACOLOGY & THERAPEUTICS, PROFESSOR, 薬学部, 教授 (60117794)
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| Co-Investigator(Kenkyū-buntansha) |
OHYA Susumu NAGOYA CITY UNIVERSITY, CHEMICAL PHARMACOLOGY, JUNIOR LECTURER, 薬学部, 助手 (70275147)
MURAKI Katsuhiko NAGOYA CITY UNIVERSITY, CHEMICAL PHARMACOLOGY, ASSOCIATE PROFESSOR, 薬学部, 助教授 (20254310)
WATANABE Minoru NAGOYA CITY UNIVERSITY, CHEMICAL PHARMACOLOGY, PROFESSOR, 薬学部, 教授 (50012638)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | smooth muscle / CaィイD12+ィエD1 activated KィイD1+ィエD1 channel / L-type CaィイD12+ィエD1 channel / CaィイD12+ィエD1 spark / CaィイD12+ィエD1-activated ClィイD1-ィエD1 current / CaィイD12+ィエD1-induced CaィイD12+ィエD1 release / cardiac atrial myocyte / ruthenium red / 負帰還機構 / Ca依存性Kチャネル / L型Caチャネル / 電流密度 / mRNA発現量 / SHR |
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| Research Abstract |
The interrelationship between the ionic current density of two channels (voltage-dependent L-type CaィイD12+ィエD1 channels (VDCCs) and large conductance CaィイD12+ィエD1 activated KィイD1+ィエD1 channels (BKCs) and the mRNA expression level of their channel subtypes (αィイD21cィエD2 subunit of L-type CaィイD12+ィエD1 channels (α1C) and α/β subunits of BK channel (αBK/βBK)) was determined in rabbit smooth muscles. BK currents (IィイD2K-CaィエD2) in the rabbit aorta were much smaller than those in the rabbit vas deferens. However, when CaィイD12+ィエD1 current (IィイD2CaィエD2) was increased by Bay K 8644, IィイD2K-CaィエD2 was also markedly increased especially in aortic smooth muscle cells. The amount of mRNA contents of encoding α1C was apparently higher in urinary bladder and vas deferens than that in aorta and trachea. In contrast, the mRNA contents of encoding both αBK and βBK were observed at similar levels in their four tissues. These observation raised the possibility that quantitative differences in the VDCC and
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BKC may provide an explanation for the differences in membrane excitability between aorta and trachea versus urinary bladder and vas deferens.
The effects of ruthenium red (RuR) on contractility were examined in skinned fibers of guinea pig smooth muscles. Contractions of skinned fibers of the urinary bladder were enhanced by RuR (ECィイD250ィエD2=60μM). The contraction at pCa 6.0 was increased to 320% of control by 100μM RuR. Qualitatively the same results were obtained in the ileal longitudinal smooth muscle layer and mesenteric artery. Maximal contraction induced by pCa 4.5 was not affected significantly by RuR. Application of microcystin, a potent protein phosphatase inhibitor, induced a tonic contraction of skinned smooth muscle at low [CaィイD12+ィエD1] (pCa >8.0). RuR had a dual effect on the microcystin-induced contraction : enhancement at low concentrations and suppression at high concentrations. The relaxation following the decrease in [CaィイD12+ィエD1] from pCa 5.0 to >8.0 was significantly slowed down by an addition of RuR. Phosphorylation of myosin light chain at pCa 6.3 was significantly increased by RuR. These results indicate that RuR markedly increases CaィイD12+ィエD1 sensitivity of the contractile system at least in part via inhibition of myosin light chain phosphatase.
Spatiotemporal relationships between CaィイD12+ィエD1 sparks and the activation of transient ClィイD1-ィエD1 current were analyzed in rabbit atrial myocytes based on simultaneous measurements of two dimensional CaィイD12+ィエD1 images by fast scanning confocal microscopy and membrane currents under whole cell voltage-clamp. The results suggest that CaィイD12+ィエD1 sparks initiate some patterns of global [CaィイD12+ィエD1]ィイD2iィエD2, and that either a CaィイD12+ィエD1 hot spot or a CaィイD12+ィエD1 wave is the spatiotemporal summation of individual CaィイD12+ィエD1 sparks, which results in the activation of CaィイD12+ィエD1 dependent ion channels on the sarcolemma. It can be strongly suggested that a CaィイD12+ィエD1 spark is a functional unit not only in excitation-contraction (E-C) coupling but also in the activation of CaィイD12+ィエD1 dependent membrane current, mainly IィイD2Cl-CaィエD2, in rabbit atrial myocytes. Less
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Report
(3 results)
Research Products
(6 results)
