Fig. 6: An epiphenomenal Ca++-current downstream of pMLKL is sensitive to dantrolene.

TNFα/zVAD/SMAC (TZS)-mimetic-induced necroptosis of HT29 cells results in a whole cell current that is sensitive to necrosulfonamide (NSA) and peaks 16 h after induction (a). The NSA-sensitive Ca++-current is sensitive to chloride-depletion (b). TZS-induced necroptosis is accompanied by a small-scale Ca++-current within 3-4 h after induction of cell death (c) which is sensitive to dantrolene and NSA (d), but dantrolene does not interfere with combined positivity to annexin V and 7-AAD (compare screen in Fig. 3c). In contrast to dantrolene, however, the phenytoin prevents the cell from dying, but does not prevent the ionomycin-induced Ca++-signal (e)