Effects of mefloquine on ER calcium homeostasis. The effects of mefloquine on cytoplasmic calcium levels in rat neurons were investigated using confocal microscopy. Neurons were loaded with the calcium-sensitive dye Fluo-3 that was replaced with low-calcium Locke's buffer after 1 h. The neurons were scanned at 10 s intervals to measure baseline fluorescence prior to the addition of DMSO (0.2%) or mefloquine (Mef, 80 μM) followed by thapsigargin (Thaps, 1 μM). Arrows indicate additions after scans 2 and 37, respectively. Mefloquine increased cytoplasmic calcium and antagonized the pharmacological action of thapsigargin, suggesting that the drug mobilizes the ER calcium store. The lack of a subsequent glutamate response (Glu, 1 μM after scan 63) demonstrates the external medium was substantially devoid of free calcium, whilst the presence of a subsequent CaCl2 (1.6 mM after scan 67) response indicates that the neurons remain viable at the termination of the experiment.