A range of voltage-clamp protocol designs for rapid capture of hERG kinetics

Lei, Chon Lok; J Whittaker, Dominic; J Windley, Monique; D Perry, Matthew; P Hill, Adam; R Mirams, Gary

Abstract

We provide details of a series of short voltage-clamp protocols designed for gathering a large amount of information on hERG (Kv11.1) ion channel gating. The protocols have a limited number of steps and consist only of steps and ramps, making them easy to implement on any patch clamp setup, including automated platforms. The primary objective is to assist with parameterisation, selection and refinement of mathematical models of hERG gating. We detail a series of manual and automated model-driven designs, together with an explanation of their rationale and design criteria. Although the protocols are intended to study hERG1a currents, the approaches could be easily extended and generalised to other ion channel currents.

Citation

Lei, C. L., J Whittaker, D., J Windley, M., D Perry, M., P Hill, A., & R Mirams, G. A range of voltage-clamp protocol designs for rapid capture of hERG kinetics

• Working Paper Type: Preprint
• Online Publication Date: Nov 12, 2024
• Deposit Date: Mar 14, 2025
• Publicly Available Date: Mar 17, 2025
• DOI: https://doi.org/10.12688/wellcomeopenres.23319.1
• Public URL: https://nottingham-repository.worktribe.com/output/41933409
• Publisher URL: https://wellcomeopenresearch.org/articles/9-673/v1
• Additional Information: Referee status: Awaiting Peer Review; Grant Information: This work was supported by the Wellcome Trust (grant no. 212203/Z/18/Z); the Science and Technology Development Fund, Macao SAR (FDCT) [reference no. 0155/2023/RIA3 and 0048/2022/A]; the University of Macau [reference no. SRG2024-00014-FHS and FHS Startup Grant]; the Engineering & Physical Sciences Research Council (EPSRC) [grant no. EP/R014604/1]; and the Australian Research Council [grant no. DP190101758]. DGW & GRM acknowledge support from the Wellcome Trust via a Wellcome Trust Senior Research Fellowship to GRM. CLL acknowledges support from the FDCT and support from the University of Macau. We acknowledge Victor Chang Cardiac Research Institute Innovation Centre, funded by the NSW Government.; This research was funded in whole, or in part, by the Wellcome Trust [212203/Z/18/Z]. For the purpose of open access, the authors have applied a CC-BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Copyright: This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.