Fig. 4: Nifedipine selectively perturbs the activation of VSD-I and -III.
From: The molecular transition that confers voltage dependence to muscle contraction
a Structure of CaV1.1 α1S interacting with nifedipine. Color code: repeat I in blue; repeat II in red; repeat III in green; repeat IV in yellow; Ca2+ ions in purple and nifedipine in black. The inset shows an enlargement of the nifedipine docking site, which includes parts of the α1S pore domain: S5III, S6III, P-loopIII, and S6IV helices. Side chains of putative residues coordinating nifedipine are shown. Red dashed lines represent potential hydrogen bonds (Protein Data Bank ID 6JP5, adapted from ref. 23). b Representative Ba2+ current traces before (black) and after 10 µM nifedipine (violet). c Normalized current-voltage relationship constructed from traces as in (b) (n = 6). d, e CaV1.1 VSD activations in the absence (“control”, d) and in the presence of 10 µM nifedipine (e). The voltage-clamp protocol is shown above the traces in panel (d). f F(V) curves for the four VSDs in the absence (circles) and presence of nifedipine (10 µM, squares). Note that nifedipine caused a leftward shift of the activation curves of VSD-I and -III, while leaving VSD-II and -IV unaffected. Data were fitted to the Boltzmann distribution. Fitting parameters are reported in Supplementary Table 3. Error bars are ± SEM (VSD-I: control n = 11, nifedipine n = 5; VSD-II: control n = 8, nifedipine n = 5; VSD-III: control n = 14, nifedipine n = 14; VSD-IV: control n = 7, nifedipine n = 7).
