Fig. 1.
NS9283 selectively promotes activation and desensitization of (α4)3(β2)2 nAChRs by varenicline. The different receptor subtypes were expressed in HEK293 cells and assayed with a membrane potential sensitive dye. In activation experiments, varenicline was added acutely whereas in desensitization studies, varenicline was preincubated with cells for 6 h prior to acute application of ACh [300 μM for (α4)3(β2)2, 10 μM for (α4)2(β2)3, 300 μM for α3β4, 100 μM for α7]. For desensitization studies with cells expressing 5HT3A receptors, varenicline was preincubated for 1 h prior to acute application of 5HT (3 μM). These preincubation times were chosen to ensure complete desensitization without significant upregulation of nAChRs or downregulation of 5HT3A receptors