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: 6019165
• 负责人: Wai-Meng Kwok
• 金额: $ 10.52万
• 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 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6019165
• 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：（改编自申请人摘要）本研究的目的 是确定吸入性和非吸入性之间相互作用的细胞机制， 麻醉药和心脏ATP敏感性钾通道（KATP）， 研究这种相互作用在缺血条件下是如何受到影响的。 围手术期心肌缺血可导致术后出现心肌缺血， 心脏和非心脏手术，但麻醉作用的机制 在缺血期间的作用还不太清楚。 之一 在局部缺血期间在心脏中发生的电生理变化是 激活KATP通道。 这些通道是由代谢 心脏的状态，并可能作为一个心脏保护机制， 缺血 因此，麻醉作用的一个潜在靶点， 缺血是KATP通道。 到目前为止，研究的影响， 吸入麻醉药在细胞水平对心脏KATP通道的影响 是有限的。 本提案中描述的实验将描述 KATP通道和吸入麻醉剂之间的相互作用， 膜片钳技术 具体目标是：（1）确定 吸入麻醉药对KATP的影响机制 2）确定麻醉作用对KATP的影响 通道在缺血条件下，和3）表征如何麻醉剂 改变钾通道开放剂激活KATP的能力 渠道 初步结果表明，吸入性麻醉剂 对KATP通道的不同影响。 因此，阐明细胞的 对KATP通道起麻醉作用的机制还远未成熟。 达到临床意义。 根据所用麻醉剂的类型， 它可以增强或减少潜在的心脏保护机制， 心脏KATP通道。