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.
