Figure 3

Dose-response curves for mefloquine's effects on neuronal cell viability and mobilization of ER calcium stores. Neurons were exposed to mefloquine (0.75–200 μM) for 5 min, 20 min or 24 h. Viability was assessed using the colorimetric MTT assay. Dose-response data is presented as mean viability (% ± SEM compared to appropriate DMSO controls) and represents data from at least three pooled experiments. For the ER-calcium experiments, changes in neuronal intracellular calcium concentrations induced in response to different mefloquine treatments were monitored in real time using confocal microscopy. Dose-response effects are expressed as a percentage of the maximal elevation of cytoplasmic calcium occurring at 200 μM mefloquine. The dose-response curves for mefloquine's effects on neuronal viability (5 min exposure) and ER calcium store mobilization are superimposable, as are the 20 min and 24 h exposure curves. At a concentration of 50 μM, mefloquine exhibited greater toxicity after 20 min and 24 h exposure as compared to 5 min exposure (one way ANOVA and Dunnett's t-test, P < 0.0001, n = 12, see asterixed points on graph). Therefore, it appears that the neurotoxic effects of mefloquine occur within 20 min of exposure, but cannot be accounted for solely by the disruptive effect of mefloquine on ER calcium homeostasis.