Figure 1. Structural basis for inhibition of Ca_VAb by amlodipine.

a, Amlodipine structure. Ba²⁺ currents for 0 nM (black) and 10 nM (red) amlodipine during depolarization from −120 mV to 0 mV. b, State-dependent block by amlodipine after 50-ms pulses at 1 Hz from −120 mV to 0 mV (10 nM, circles; 100 nM, triangles; mean ± s.e.m.; n = 3–5. c, Inhibition by amlodipine. Data were fit by the Hill equation with n_H = 1. Ca_VAb: IC₅₀ = 10 ± 0.4 nM; Ca_VAb I199S: IC₅₀ = 112 ± 10 nM; n = 3–5; mean ± s.e.m. d, Structure of Ca_VAb (top view in cylinders) binding amlodipine (yellow sticks). PM, pore module; VSD, voltage-sensing domain. e, Ca_VAb with bound amlodipine in side view. f, Dihydropyridine-binding pocket of Ca_VAb with the F_o–F_c electron density map (2.5σ, cyan) and amlodipine (yellow sticks). Ca_VAb residues contacted by amlodipine are highlighted in colours and labelled.