| Project/Area Number |
12670050
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General physiology
|
|---|
| Research Institution | Fukuoka University |
|---|
Principal Investigator |
AKIRA Uehara School of Medicien, Fukuoka University research Assistant, 医学部, 助手 (60140745)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
|---|
| Keywords | Heart / Sarcoplasmic reticulum / Ryanodine receptor / Calcium |
|---|
| Research Abstract |
Performing the two-year project on "Electrophysiological study on the cardiac ryanodine receptor (RyR) operating the Ca-induced Ca-release mechanisms", we obtained the following results. The single-channel activity from the cardiac RyR was reconstituted into planar lipid bilayers.
(1) We explored a modulation mechanism of the channel activity of the RyR via a phosphorylation. The RyR was activated by the protein kinase A subunit. The phosphorylated RyR channels open/close more frequently, stay open longer, stay closed for shorter periods. It was improved that the activation is ascribable to the decrease in sensitivity to the cytosolic blocking ligarid of Mg ion. A paper on this work was recently accepted by Pflugers Archiv.
(2) We investigated another modulation mechanism of the channel activity of the RyR by the pathophysiological metabolytes from membrane lipids such as sphingolipids. Although this substance is lipid, it is likely to bind to the specific cytoplasmic site of the channel molecule and to block the channel activity. A paper on this work was already submitted to some journal.
(3) We also analysed the inactivation mechanism of the real current of the RyR to inhibit the Ca-induced Ca-release. We are now preparing a paper on this work.
Thus, some novel regulation mechanisms by cytoplasmic metabolites of the cardiac myocytes on RyR which exerts a central role of the Ca-induced Ca release have been elucidated.
|
