ANESTHETIC ACTION ON THE ATP-SENSITIVE POTASSIUM CHANNEL

对 ATP 敏感的钾离子通道的麻醉作用

• 批准号: 6181035
• 负责人: Wai-Meng Kwok
• 金额: $ 10.9万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6181035
• 关键词: acidosis; adenosine triphosphate; anesthetics; cyclic AMP; cytoprotection; cytotoxicity; drug adverse effect; guinea pigs; halothane; heart cell; heart electrical activity; heart metabolism; inhalation anesthesia; intermolecular interaction; isoflurane; lactates; muscle cells; myocardial ischemia /hypoxia; myocardium; phosphorylation; potassium channel; second messengers; voltage /patch clamp

DESCRIPTION: (Adapted from the applicant's abstract) The goal of this study is to identify the cellular mechanism of interaction between inhalational anesthetics and the ATP-sensitive potassium channel (KATP) in heart and to investigate how this interaction is affected during ischemic conditions. Perioperative myocardial ischemia can result in deleterioius effects after both cardiac and noncardiac surgery, but the mechanisms of anesthetic action during the ischemic period are not well understood. One of the electro-physiological changes that occur in the heart during ischemia is activation of KATP channels. These channels are gated by the metabolic state of the heart and may serve as a cardioprotective mechanism during ischemia. Consequently, a potential target of anesthetic action during ischemia is the KATP channel. To date, studies of the effects of inhalational anesthetics on the KATP channel in heart at the cellular level are limited. The experiments described in this proposal will characterize the interaction between the KATP channel and inhalational anesthetics using the patch clamp methodology. The specific objectives are 1) to determine the mechanism of the effects of inhalational anesthetics on the KATP channels; 2) to determine the effects of anesthetic action on the KATP channels during ischemic conditions, and 3) to characterize how anesthetics alter the ability of potassium channel openers to activate the KATP channels. Preliminary results show that inhalational anesthetics exert differential effects on the KATP channel. Thus, elucidation of the cellular mechanism responsible for anesthetic action on the KATP channel has far reaching clinical significance. Depending on the type of anesthetic used, it may enhance or reduce the potentially cardioprotective mechanism of the KATP channel in heart.

描述：（改编自申请人的摘要）本研究的目的