Fig. 7. Working model of presynaptic mechanism of isoflurane in  Caenorhabditis elegans . Diacyl glycerol (DAG;  green circle ) is known to bind to UNC-13 (  blue rounded rectangle ) and thereby increase the local concentration of UNC-13 at the presynaptic membrane.  23,32,33,62Membrane translocation of UNC-13 is thought to promote interaction with syntaxin and thereby promote fusion of synaptic vesicles and transmitter release. Isoflurane (  orange triangle ) antagonizes DAG-mediated membrane translocation of UNC-13, and myristoylated UNC-13, which promotes transmitter release in a DAG-independent manner  23,62and confers isoflurane resistance (  figs. 5 and 6and  table 2). Animals without UNC-13 are highly isoflurane resistant (  fig. 4). These three results can be explained by isoflurane binding to UNC-13 and antagonizing DAG binding or the effect of binding (indicated by  crossed-out arrow ). Truncated syntaxin (  red rectangle ), which lacks its transmembrane domain, blocks isoflurane sensitivity (  fig. 1), presumably by competing with isoflurane for binding to UNC-13 (indicated by  crossed-out arrow ) because UNC-13 overexpression can suppress the isoflurane resistance of truncated syntaxin. 

Fig. 7. Working model of presynaptic mechanism of isoflurane in  Caenorhabditis elegans . Diacyl glycerol (DAG;  green circle ) is known to bind to UNC-13 (  blue rounded rectangle ) and thereby increase the local concentration of UNC-13 at the presynaptic membrane.  23,32,33,62,Membrane translocation of UNC-13 is thought to promote interaction with syntaxin and thereby promote fusion of synaptic vesicles and transmitter release. Isoflurane (  orange triangle ) antagonizes DAG-mediated membrane translocation of UNC-13, and myristoylated UNC-13, which promotes transmitter release in a DAG-independent manner  23,62 and confers isoflurane resistance (  figs. 5 and 6,and  table 2). Animals without UNC-13 are highly isoflurane resistant (  fig. 4). These three results can be explained by isoflurane binding to UNC-13 and antagonizing DAG binding or the effect of binding (indicated by  crossed-out arrow ). Truncated syntaxin (  red rectangle ), which lacks its transmembrane domain, blocks isoflurane sensitivity (  fig. 1), presumably by competing with isoflurane for binding to UNC-13 (indicated by  crossed-out arrow ) because UNC-13 overexpression can suppress the isoflurane resistance of truncated syntaxin. 

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