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. 2017 Feb 1;37(5):1162–1175. doi: 10.1523/JNEUROSCI.2181-16.2016

Figure 6.

Figure 6.

Bidirectional modulation of GABAB-activated Kir3 currents by KCTD hetero-oligomers. A, Representative baclofen-activated K+ current traces recorded at −50 mV from CHO cells expressing GABAB receptors and Kir3.1/3.2 channels either without KCTD (without [w/o], gray trace), with KCTD12 alone (black), with KCTD16 alone (blue), or with both KCTDs (red). KCTD12, but not KCTD16, induces pronounced and rapid desensitization of K+ currents. Coexpression of KCTD12 and KCTD16 results in intermediate current desensitization. B, Baclofen-activated K+ currents recorded from CHO cells either expressing KCTD12 (black), a KCTD16 mutant lacking the T1 domain (16ΔT1, blue), or both KCTD isoforms (red). Expression of KCTD12 together with 16ΔT1, which only binds to the receptor in a complex with KCTD12, reduces KCTD12-induced desensitization. C, Bar graph summarizing the relative desensitization of baclofen-activated K+ currents. The relative desensitization was calculated as follows: (1 − (ratio of current amplitude after 60 s vs peak current)) × 100. Values are mean ± SD of 26 (w/o KCTD), 17 (KCTD12), 14 (KCTD16), 11 (16ΔT1), 6 (KCTD12/KCTD16), and 13 (KCTD12/KCTD16ΔT1) cells. D, Normalized traces represent a slower time course of K+ current desensitization in CHO cells coexpressing KCTD12 and 16ΔT1 (red) compared with CHO cells expressing KCTD12 alone (black). Traces are fitted to a double exponential function (gray solid line) with time constants τ1 = 1.0 s (relative contribution to desensitization 71.7%) and τ2 = 9.4 s for KCTD12 and τ1 = 3.9 s (33.8%) and τ2 = 28.4 s for KCTD12/KCTD16ΔT1. E, Bar graph showing mean amplitude-weighted time constants obtained from fits of a double exponential function to K+ current deactivation. F, Superimposed traces of the deactivation phase of K+ currents activated by application of baclofen to CHO cells for 1 min as in A or B displayed with an expanded time scale. KCTD12 and KCTD16 have opposite effects on the time course of the deactivation, with KCTD12 being dominant when coexpressed with KCTD16. G, Bar graph summarizing the time constants obtained from a fit of the K+ current deactivation to a single exponential function. H, Representative traces of K+ currents activated by baclofen (2 s) to CHO cells expressing no KCTD (w/o, gray), KCTD12 alone (black), 16ΔT1 alone (blue), or both KCTDs (red). KCTD12 neither reduces the effect of 16ΔT1 nor accelerates deactivation of brief current responses. I, Bar graph showing mean time constants obtained from fits of current deactivation to a one exponential function. Data are collected from 12 (w/o KCTD), 11 (KCTD12), 6 (16ΔT1), and 6 (KCTD12/KCTD16ΔT1) experiments. *p < 0.05 (Dunnett's multiple-comparison test and Bonferroni pairwise comparison test). **p < 0.01 (Dunnett's multiple-comparison test and Bonferroni pairwise comparison test). ***p < 0.001 (Dunnett's multiple-comparison test and Bonferroni pairwise comparison test).