To address the possibility that the Clic genes exc-4 and exl-1 might work in concert, we also assessed the behavioral response to ethanol in exc-4;exl-1 double mutants. Interestingly, initial sensitivity in the double mutants was essentially normal (similar to exl-1 mutants), whereas acute tolerance was significantly suppressed in these animals (similar to exc-4 mutants) (Figure 5A). Since internal ethanol concentrations were not significantly altered in exc-4(rh133);exl-1(ok857) double mutants compared to wild-type N2 controls (Figure 5B), we tentatively conclude that the effect of loss of exc-4 function on initial sensitivity requires normal expression of exl-1 and conversely that the effect of loss of exl-1 function on acute tolerance requires normal expression of exc-4.
