1998 Fiscal Year Final Research Report Summary
Combined Effects of Acidosis, Hypoxia, and Anesthetics on the K_<ATP> Channels in Isolated Rat Myocytes.
| Project/Area Number |
09671568
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | Tokushima University |
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Principal Investigator |
OSHITA Shuzo Tokushima University, Medicine, Professor, 医学部, 教授 (60144945)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAYA Yutaka Tokushima University, Nutrition, Professor, 医学部, 教授 (50136222)
KITAHATA Hiroshi Tokushima University, Medicine, Assistant Professor, 医学部, 助教授 (60161486)
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| Project Period (FY) |
1997 – 1998
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| Keywords | ventricular myocytes / ATP sensitive potassium channel / anesthetics |
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| Research Abstract |
Using patch clamp technique we investigated the effects of anesthetics on the ATP sensitive potassium (K_<ATP>) channels in rat ventricular myocytes. Since the activation of the K_<ATP> channels is caused by intracellular ATP depletion, we used DNP (an inhibitor of mitochondrial ATP synthesis) or ATP-free solution to simulate ischemia. In both cell-attached and inside-out configurations, the K_<ATP>, channel activities were suppressed by thiamylal in a concentration-dependent manner. These data suggest that thiamylal inhibits the K_<ATP> channels directly. Furthermore, this blockade was reversible, thus we could observe the reappearance of the channel activities by washing out thiamylal. Then, we studied the effects of thiamylal on the K_<ATP> channel activities using acidotic bath solution (pH=6.5) instead of DNP solution. Thiamylal also inhibited the K_<ATP> channels in aciotic solution. We also studied the interaction of other anesthetics with the K_<ATP> channels, using the same methods as described above. Volatile anesthetics (1 MAC of halothane, isoflurane and sevoflurane) caused reductions in the activities of the K_<ATP>, channels but propofol did not affect the channel activities. Results obtained from controlled animal experiments must be viewed with appropriate caution when extrapolating to the clinical situation. The results obtained in this study suggest that thiamylal and volatile anesthetics may inhibit the cardioprotective effects of the K_<ATP> channels during myocardial infarction.
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