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Combined Effects of Acidosis, Hypoxia, and Anesthetics on the K_<ATP> Channels in Isolated Rat Myocytes.

Research Project

Project/Area Number 09671568
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionTokushima University

Principal Investigator

OSHITA Shuzo  Tokushima University, Medicine, Professor, 医学部, 教授 (60144945)

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)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
Keywordsventricular myocytes / ATP sensitive potassium channel / anesthetics / ATP感受性Kチャンネル
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.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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