Figure 10
D2L5 and D4L6 extracellular loops regulate the degree of Ca2+ block of the Na+ current and the fold increase in relative peak Ca2+ current size when external Ca2+ rises from 10 µM [Ca2+]ex to the physiological (mM) range. (A) Normalized peak current sizes in response to increasing concentrations of [Ca2+]ex from 10–9 to 10–2 M in presence 60 mM [Na+]ex for wild type snail LCaV3–12a and LCaV3–12b channels, and chimeric snail LCav3 channels with D2L5 and D2L6 extracellular loops from human Cav3.2. (B) Bar graphs of the normalized peak current blockade at 10 µM [Ca2+]ex, the maximally effective blocking Ca2+ concentration for human Cav3 channels (i.e. bottom of “U” shaped curve in A). (C) Bar graphs of the fold change in normalized peak currents from 10 µM to 10 mM [Ca2+]ex. Graphs illustrate mean ± SEM with replicates (n) illustrated as grey diamonds. Data to generate graphs were compared in a parametric one-way ANOVA with a Tukey post hoc analyses to test for statistical significances. Statistical significances are tabulated in Supplementary Tables S8 and S9 for (B,C). Data are significant (p < 0.01), unless stated, where n.s.non-significant. Data for LCaV3–12b, LCaV3–12a and Cav3.1 in this figure are reproduced integrally from Senatore et al.9. Color coding of differing Cav3 channels: Cav3.2 (dark blue), LCaV3–12b (orange), LCaV3–12a (red), LCav3 Δcys mutants (striped orange or red bars), snail LCav3 or human Cav3.2 channels with chimeric extracellular loops (light purple). Data contained in this figure were analyzed and illustrated using OriginPro 2018 (64-bit) SR1 b9.5.1.195.
