1999 Fiscal Year Final Research Report Summary
Inactivation mechanisms of voltage-gated Ca channels by CaィイD12+ィエD1 in smooth muscle cells.
| Project/Area Number |
10660283
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Basic veterinary science/Basic zootechnical science
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| Research Institution | Gifu University |
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Principal Investigator |
OHASHI Hidenori Gifu University, Faculty of Agriculture, Professor, 農学部, 教授 (40001531)
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| Co-Investigator(Kenkyū-buntansha) |
KOMORI Seiichi Gifu University, Faculty of Agriculture, Professor, 農学部, 教授 (70195866)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Smooth muscle / Voltage-gated Ca channel / Muscarinic receptor / Patch clamp / Phospholipid metabolism / Phospholipase / Microtubule cytoskeleton / protein kinase |
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| Research Abstract |
Voltage-gated Ca channels in smooth muscle cells are the most important pathway for allowing CaィイD12+ィエD1 to flow down a concentration gradient into the cell. In the present study, we explored the inactivation mechanisms of voltage-gated Ca channels using the whole-cell patch clamp technique. Outlines of the obtained results are as follows.
1. Carbachol (acting at muscarinic receptors) or histamine (acting at H1 histamine receptors) suppressed voltage-gated Ca channel currents (IィイD2CaィエD2) evoked by depolarizing pulses in a biphasic manner, an initial transient component followed by a sustained component. The possibility that phospholipid metabolisms are implicated in the biphasic suppression of IィイD2CaィエD2 was examined using inhibitors of phospholipases, such as wortmannin and D609. The results show that phospholipase C is involved in the transient component of IィイD2CaィエD2 suppression, and phospholipase C or D in the sustained component of IィイD2CaィエD2 suppression.
2. To see if cytoskeletons, such as actin microfilaments and microtubules, are involved in the biphasic suppression of IィイD2CaィエD2 induced by carbachol, effects of cytoskeletal depolymerizers and polymerizers on the carbachol action were investigated. The results sugget that the bipbasic suppression of IィイD2CaィエD2 is mediated by microtubule polymerization.
3. The possibility thet phosphorylation of Ca channels is implicated in the biphasic suppression of IィイD2CaィエD2 was examined using inhibitors and activators of protein kinase A, protein kinase G, protein kinase C and calmodulin dependent myosin light chain kinase. The results suggest that phosphorylation process is not involved in the biphasic suppression of IィイD2CaィエD2.
The above results have been published as 2 papers in the Britishi Journal of Pharmacology. How muscarinic receptor stimulation polymerizes microtubules, and how microtubule polymerization suppress voltage-gated Ca channel activity will be examined.
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Research Products
(4 results)
