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. 2018 Feb 26;8:3643. doi: 10.1038/s41598-018-22033-1

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Ranolazine effects on fast inactivation onset time constants. Panels A,B show the single-exponential time constants plotted against voltage. The pulse protocol is identical to that used to measure channel conductance (refer to Methods). Panel C includes Q₁₀ coefficient values for all conditions between −50 mV to +10 mV. Cytosolic calcium seems to modulate Ranolazine effects on WT Q₁₀, as elevated cytosolic calcium heightened thermosensitivity. Cytosolic calcium made −50 mV fast inactivation onset in E1784K less thermosensitive, consistent with decoupling between CTD and Domain III-IV linker mechanism, explained in the discussion.