Volatile anesthetic represent some of the most clinically important drugs in currents use. They are used to produce reversible interruption of consciousness and thereby induce insensitivity to pain and other sensory stimulation. Clearly, anesthetic must interfere with the proper function of precesses fundamental to the operation of synapses involved in perception. Thus, the study of their action has great promise for elucidating important neurophysiologic functions. Another striking aspects of anesthetic action is that, unlike other drugs, anesthetics display a remarkable constancy of effect and potency over enormous evolutionary span. This fact suggests that the site of action of anesthetics has been highly conserved. We have made use of this observation by studying the effect of anesthetics in the well defined nervous system of the mollusc, Aplysia californica. As a results of our initial experiments, we have found that anesthetics silence certain spontaneously firing neurons in Aplysia by a mechanism that involves activation of a voltage-independent potassium channel. We have identified this channel as the S-K+ channel by several criteria. Currently, we are investigating the mechanism by which this activation occurs. This characterization will lead to isolation of the ion channel by molecular cloning that in turn will allow us to search for related ions channels in the far more complex mammalian central nervous system. This propose research is important from three perspectives: (1) it will help elucidate the molecular basis of general anesthetic action; (2) it will lead to a greater understanding of the operation of synapses in the CNS; (3) it will help in the development of more specific anesthetics.
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