1999 Fiscal Year Final Research Report Summary
Mechanism of metabolites produced by and protective drugs against ischemia-reperfusion injury in ventricular myocytes.
| Project/Area Number |
10670078
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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 |
General pharmacology
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| Research Institution | AKITA UNIVERSITY (1999)
Asahikawa Medical College (1998) |
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Principal Investigator |
YAZAWA Kazuto School of Medicine, akita Univeersity, Lecturer, 医学部, 講師 (90212274)
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| Project Period (FY) |
1998 – 1999
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| Keywords | calcium current / lysophosphatidylcholine / ventricular myocytes / patch clamp method / guinea-pig |
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| Research Abstract |
Lysophosphatidylcholine (LPC), an amphiphilic metabolite of membrane phospholipids, accumulates in cardiac tissue during ischemia and reperfusion. LPC produces arrythmia, although the effect for ion channels is not fully understood under the physiological and pathophysiological conditions. The aim of this study was to investigate the mechanisms underlying the effect of LPC on CaィイD12+ィエD1 current (IィイD2CaィエD2 under these conditions in single ventricular cells using the whole-cell patch clamp method.
Single ventricular myocytes of a female guinea-pig (300-600g) were prepared by using a Langendorff method. The concentration of CaィイD12+ィエD1 in the pipette solutions at pH 7.4 and pH 6.4 were pCa 8. The external solutions were warmed by water jacket before being put into the recording chamber ; all experiments were performed at 35-37℃.
The results were followed : 1. LPC reduced IィイD2CaィエD2 under the physiological and pathophysiological pH ; 2. The sensitivity of IィイD2CaィエD2 for LPC was increased under acidic conditions ; 3. Although LPC caused depression of IィイD2CaィエD2 without affecting the activation curve or the steady-state inactivation curve at physiological pH, LPC shifted them in the negative direction at pathophysiological pH.
These results suggest the following possibilities ; 1. protons increase the inhibitory effect of LPC on IィイD2CaィエD2 ; 2. LPC might increase the proton sensitivity of the inside membrane, or decreases the proton sensitivity of the outside membrane.
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