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Information

  1. Pharmacologic Approaches. An experimental paradigm frequently used to study anesthetic mechanisms is to administer a drug thought to act specifically at a putative anesthetic target (a receptor agonist or antagonist, an ion channel activator or antagonist) and then determine whether the drug has either increased or decreased the animal's sensitivity to a given anesthetic. Development of specific antagonists for anesthetic agents would provide a major tool for linking anesthetic effects at the molecular level to anesthesia in an intact organism and might also be of significant clinical utility.
  2. Genetic Approaches. An alternative approach to study the relationship between anesthetic effects observed in vitro and whole-animal anesthesia is to alter the structure or abundance of putative anesthetic targets and determine how this affects whole-animal anesthetic sensitivity.
    1. There has been a focus on a novel presumptive cation channel, NCA-1/NCA-2, that controls halothane sensitivity in both Caenorhabditis elegans and the fruit fly Drosophila.
    2. In mammals, the most powerful genetic model organism is mouse, in which techniques have been developed to alter or delete any gene of interest. The GABAA receptor has been extensively studied using mouse genetic techniques.

Outline

Mechanisms of Anesthesia and Consciousness

  1. What is Anesthesia?
  2. How is Anesthesia Measured?
  3. What is the Chemical Nature of Anesthetic Target Sites?
  4. How Do Anesthetics Interfere with the Electrophysiologic Function of the Nervous System?
  5. Anesthetic Actions on Ion Channels
  6. How are the Molecular Effects of Anesthetics Linked to Anesthesia in the Intact Organism?
  7. Where in the Central Nervous System Do Anesthetics Work?
  8. Conclusions