Figure 5.
Evidence for CAMKII-dependent activation of TMEM16A but not for CAM- or calcineurin-dependent regulation of endogenous TMEM16A in CFBE airway epithelial cells. (A) Whole cell patch clamp analysis of ATP (100 µM)-activated TMEM16A currents and effects of the 1-EBIO analogues DCEBIO and riluzole (both 10 µM), the CAMKII-inhibitors KN-62 and KN-93 (both 10 µM) and the calcineurin inhibitor tacrolimus (10 µM). Cells were pre-incubated with the compounds, which were also present during the experiment. Under all conditions, significant activation of whole cell currents by ATP was observed. While the KCNN4 activators DCEBIO and riluzole enhanced ATP-activated currents, KN-62, KN-93, and tacrolimus reduced current activation. The time course for ATP-activation of TMEM16A remained unchanged by the drugs. (B) Calculated current densities. All experiments were performed in the presence of the KCNN4-inhibitor TRAM-34. Mean ± SEM (n = number of experiments). * Significant activation by ATP (p < 0.05; paired t-test).