Figure 4

Effects of mefloquine on whole cell calcium homeostasis and their antagonisation by thapsigargin. The effects of mefloquine on neuronal whole cell calcium homeostasis were investigated using confocal microscopy and Locke's buffer containing physiological calcium levels (2.3 mM). Neurons were loaded with the calcium-sensitive dye Fluo-3 that was replaced with normal Locke's buffer after 1 h. Neurons were scanned at 15 s intervals. Mefloquine (MEF80, 80 μM), thapsigargin (THAPS, 4 μM) or DMSO (0.4%) were added at scan 13 (as indicated by the first arrow). Subsequently (second arrow at scan 28), DMSO (0.2%) or mefloquine (80 μM) were added. Mefloquine (but not DMSO) caused an immediate and sustained rise in the cytosolic calcium concentration. This elevation is due to an influx across the plasma membrane as it was not observed in neurons bathed in low calcium Locke's buffer. The effect was antagonized by prior treatment with thapsigargin. As this agent is a specific inhibitor of the ER calcium pump, the data suggest that the effects of mefloquine on calcium homeostasis are mediated at the level of the ER in rat neurons.