Extended Data Fig. 7: Voltage-independent spHCN-M375L channels are blocked by the specific HCN channel blocker ZD7288 and the Met375-Phe459 interaction is important to close spHCN channels at positive voltages.
From: Propofol rescues voltage-dependent gating of HCN1 channel epilepsy mutants
a, Representative current traces from spHCN M375L channels before (left) and after (right) the application of 100 µM ZD7288. Dashed lines indicate no currents. Met375 and Phe459 mutants show currents at positive voltages and similar voltage sensor movement. b, GV and c, FV relations from WT (black), M375L (blue), M375F (purple), M375A (green), M375C (orange) and M375S (pink) mutant spHCN channels. d, GV and e, FV relations from WT (black), F459Y (pink), F459C (orange), F459M (purple), F459E (cyan), F459A (green), F459L (blue), F459Q (gray), F459V (magenta) and F459W (dark yellow) mutant spHCN channels. f, Representative current traces from oocytes expressing WT, M375F, F459M and M375F/F459M spHCN channels. Dashed lines indicate no currents. g, GV relations from WT (black), M375F (green), F459M (orange) and M375F/F459M (red) spHCN channels. All GV1/2, FV1/2 and n numbers are shown in Extended Data Table 2. Data are represented as mean ± s.e.m. n indicates the number of biological replicates.
