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. 2016 Jun 30;11(1):34–45. doi: 10.1080/19336950.2016.1207023

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© 2017 The Author(s). Published with license by Taylor & Francis

This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

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Figure 5. — The additive effects on channel activation due to the flexible IVS3-S4 linker and DCT/CaM competition. (A) Two different mechanisms that modulate the voltage-dependent activation of Ca_V1.3 channels. In addition to the IVS3-S4 linker where the flexibility presumably modulates the function of VSD, Ca_V1.3 channels are also subject to the competitive tuning between DCT and CaM for which the channel activation is dependent on whether CaM is preassociated with the channel. Both G_X linker (increasing flexibility) and competitive DCT (kicking-off apoCaM) would cause the positive shift of channel activation. (B and C) Exemplar traces for different combinations of G_X and DCT effects. The native form of α_1DE32_1DΔ (G₀ CaM+) contains a DCT motif with much weaker strength in competition with CaM than DCT from α_1F (DCT_F). E29_1SAllG consists of the linker from exon 29 of α_1S but with glycine substitutions (G₁₉ CaM+). α_1DΔE32_1DΔ-DCT_F (G₀ CaM-) is the chimeric channel fused with DCT_F to α_1DΔ, essentially replacing the DCT of the native form in α_1DE32_1DΔ (G₀ CaM+). α_1DΔE29_1SAllG-DCT_F (G₁₉ CaM-) is to incorporate DCT_F while containing the G₁₉ linker within the loop. Experimental conditions and color schemes are similar to Figure 1B. (C and D) Comparison among the voltage dependence of the activation curves, for the 4 kinds of channels under tests. Activation curves (C) and statistics of V_1/2 values (D) are shown for each channel subtypes. *, p < 0.05; ***, p < 0.001.