Amyloid-β_1-42 (Aβ_1-42) is believed to play a central role in the etiology of Alzheimer’s disease due to its accumulation in the brains of patients and its toxic effect on neurons. Reactive oxygen species, membrane perturbation and loss of ionic homeostasis, particularly that of Ca²⁺, have been implicated in the mechanism of toxicity (Mattson et al, 1992). Aβ_1-42 interacts with a number of receptors and channels, including those permeable to Ca²⁺, such as nicotinic acetylcholine receptors (nAChR; Dougherty et al, 2003) and voltage operated calcium channels (VOCC; Ueda et al, 2003). Upon activation, nAChR allow Ca²⁺ and Na²⁺ entry. Amplification of this Ca²⁺ signal can occur by the depolarization that can open VOCC or by calcium–induced calcium release, depending on the nAChR subtype (Dickinson et al, 2006). Aβ_1-42 has been variably reported to act as an agonist or an antagonist at nAChR (Liu and Wu, 2006). Aβ_1-42 also directly affects VOCC to increase Ca²⁺ signals, when applied chronically (Ueda et al, 2003). This study investigates the acute effects of Aβ_1-42 on intracellular Ca²⁺ produced from nAChR activation in the PC12 cell line. Aβ_1-42 was treated with trifluoroacetic acid for 30 min to encourage oligomer formation, replicating the proposed toxic form. Toxicity was confirmed by treating PC12 cells with 10 μM Aβ_1-42 for 24 h: this produced a 30 % decrease in MTT reduction when compared with vehicle-treated controls (n=6, p<0.001). When applied acutely to cells loaded with Fluo-3, Aβ_1-42 (0.1 pM – 100 nM) alone produced no increase in intracellular Ca²⁺ signal, even in the presence of PNU 120596, an allosteric modulator used to amplify nAChR activity. This suggests that Aβ_1-42 does not affect Ca²⁺ levels directly when applied acutely. However, a 10 min incubation with Aβ_1-42 potentiated nicotine-evoked increases in Ca²⁺ (2.5-fold, n=3, p>0.05). This was fully blocked by mecamylamine (20 μM) and by the VOCC-antagonist verapamil (10 μM). An interaction with VOCC was supported by the potentiation of KCl-evoked increases in Ca²⁺ (1.9-fold, n=3, p<0.01) that was also blocked by verapamil (10 μM). This suggests that Aβ_1-42 potentiates Ca²⁺ influx downstream of nAChR, by increasing the activity of VOCC.