Fig. 1.

κM-RIIIJ blocks homomeric and heteromeric Kv1 channels. (A) Schematic representation of all possible combinations between two different K_v1 subunits. Homomeric and heteromeric channels containing K_v1.2 α-subunits and a second other K_v1 family (K_v1.x) subunit are displayed. Similar combinations are possible for all K_v1.x subunits with up to four different subunits forming a functional channel. (B) κM-RIIIJ block of homo- and heterodimeric K_v1 channels. Current traces in control (black) and in the presence of κM-RIIIJ (red) are shown. (Left) At 1 µM, κM-RIIIJ blocks homomeric K_v1.1 and K_v1.6 with low apparent affinity (IC₅₀ ∼ 3–5 µM), whereas it displays ∼10× higher potency for K_v1.2 homomers (IC₅₀ ∼ 300 nM). (Right) Representative dimeric channel-mediated currents in control and 100 nM κM-RIIIJ evidencing stronger block of K_v1.2/1.1 and K_v1.2/1.6 channels. Due to extreme differences in apparent affinity, 50 nM κM-RIIIJ is shown for K_v1.2/1.1 and 2 μM for K_v1.2/1.4. Dashed lines indicate zero current. (Scale bars, 500 pA and 10 ms.) (C) κM-RIIIJ affinity toward Kv1.2-containing dimeric K_v1 channels. The bar diagram presented summarizes κM-RIIIJ IC₅₀s for dimeric constructs in forward or reversed order. In comparison with homomeric K_v1.2 channels, κM-RIIIJ has a 10- to 20-fold higher affinity for heterodimeric channels composed of K_v1.2 and either K_v1.1 or K_v1.6 subunits. All other dimeric constructs are blocked similarly or less strongly than homomeric K_v1.2. The order of the subunits in the concatemers bears no major influence on κM-RIIIJ’s activity.