Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a Cl^– channel that plays an important role in Cl^– secretion. In the airway CFTR function is regulated by an interaction with annexin-2 and S100A10 (1). This complex is also known to be important in regulating the epithelial Ca²⁺ channels TRPV5 and TRPV6 (2). A recent study has demonstrated that the annexin-2 / S100A10 interaction is lost in CF airway cells (3). Given the fact that TRPV channels are also found in airway, this suggests that Ca²⁺ handling could be altered in CF airway cells. Calcium uptake was measured in 16HBE14o- and CFBE41o- cells grown in 12-well multi-well plates. The buffer solution contained (in mM): 140 NaCl, 5 KCl, 2 CaCl₂, 1 MgCl₂, 10 HEPES, 10µM felodipine and 10µM verapamil (to inhibit voltage-gated Ca²⁺ channels). Cells were exposed to this solution for 40 minutes, with Ca⁴⁵ (5µCi/ml) added during the final minute. 10µM forskolin (FSK) and 100µM (IBMX) were added during the last 30 minutes. Cells were washed, lysed and Ca⁴⁵ uptake analysed using direct DPM scintillation counting. This was repeated in the presence of 5nM cypermethrin or 100μM ruthenium red (RR). All treatments were day matched and values are expressed as means ± SEM. Statistical significance was tested using the unpaired Students t-test or ANOVAs and assumed at the 5% level. Day matched CFBE41o- cells demonstrated greater Ca²⁺ uptake versus 16HBE14o- cells, 245 ± 17.7 pg/10⁵ cells (n=24) versus 199 ± 18.8 pg/10⁵ cells (n=24), respectively. Ca²⁺ uptake in both cell types was inhibited in the presence of cypermethrin or RR, Table 1. These data indicate that in both 16HBE14o- and CFBE41o- cells Ca²⁺ uptake is dependent on a cypermethrin and RR sensitive pathway, which may be attributable to TRPV6. Ca²⁺ uptake was greater in CF cells, suggesting that CFTR plays a role in regulating Ca²⁺ handling. Further work is needed to elucidate the pathway regulated by CFTR and the molecular mechanisms underlying this process.