Fig. 2. Subunit composition determines channel inactivation kinetics. Panels A-C illustrate different inactivation kinetics of currents measured in LRRC8 knockout cells transfected with the indicated subunits (modified from [7]; applied voltages range from -120 to 120 mV). In native cells, inactivation kinetics of VRAC is variable between cell types, but consistent for a given cells type. Panels D and E show example recordings from U87 glioblastoma cell with extremely fast inactivation, from a Panc-1 (pancreatic duct cancer cell line) cell with very slow inactivation (applied voltages range from -120 to 120 mV). Panel F highlights the structural loops identified by Ullrich et al. [19] to be determinants of inactivation kinetics. One of the 6 subunits is shown in light blue, expect the C-terminal half of the first extracellular in red. The residue corresponding to D102 of LRRC8C that is a major determinant of inactivation [19] is shown in space fill in green. It is the most "extracellularly" exposed residue. R103, which defines the narrowest part of the pore is shown in space fill in pink (pdb: 6djb, [13]).