Fig. 5: Modulation of open-state inactivation.
From: Molecular insights into the gating mechanisms of voltage-gated calcium channel CaV2.3
a Interaction of the AID between the negatively charged domains on S6II (S6IINCD) and S4-S5II. The CaV2.3 α1E subunit is shown as cartoon. The S6IINCD is overlaid as red spheres. b Zoomed-in view of the side-chain interactions among S6IINCD, AID, and S4-S5II. The S6IINCD (715DEQEEEE721) is shown as sticks. Residues involved in charge interactions on AID and S4-S5II are also shown as sticks. Negatively charged residues within the S6IINCD are highlighted using red labels. c Sequence alignment of the interaction sites among CaV1 and CaV2 members. Secondary structures are labeled over the sequences. Mutation sites are indicated by arrows. Residues with positively- and negatively charged sidechains are highlighted by blue and red, respectively. d Ratio of open-state inactivation (R200) at 10-mV test pulses, measured using the mean current at the end of the 200-ms test pulse divided by the peak amplitude. WT, n = 6; CaV2.3NQ, n = 10; R590E, n = 6; R590Q, n = 10; R378E, n = 6; R378Q, n = 9; R371E, n = 6; R371Q, n = 9. Data are plotted as box plots. The box encompasses the interquartile range (25th–75th percentile). Whiskers illustrates the minima and maxima of the values. Mean values and medians are indicated using plus signs and dashes, respectively. Significances were determined using two-sided, unpaired t test. P values, CaV2.3 WT vs. mutants; 0.01 (CaV2.3NQ), 0.005 (R590E), 0.02 (R590Q), 0.004 (R371E), and 0.004 (R378Q). n biological independent cells.
