Optimal experimental designs for characterising ion channel gating by filling the phase-voltage space of model dynamics

Mirams, Gary R; Clerx, Michael; Whittaker, Dominic G; Lei, Chon Lok

Abstract

Voltage-clamp waveforms are imposed in the patch-clamp electrophysiology technique to provoke ion currents, the particular waveform that is used is known as the “voltage-clamp protocol”. Designing protocols to probe and quantify how gating for a particular ion channel occurs has typically been done manually and results in a suite of long protocols. It is desirable to gain the same, or even more, information in a shorter time, and also to automate the process of designing these protocols. In this paper we introduce a new optimal experimental design objective for ion channel characterisation, which involves considering a 3-dimensional phase space for the channel states combined with the voltage, using room-temperature hERG/Kv11.1 currents as an example. A range of designs are proposed, the best of which visits 82% of the discretised phase-voltage space in a 9 s protocol. This new protocol design strategy results in a simulated current visiting a wide range of channel gating states, at a wide variety of voltages, and we therefore expect these designs to be very useful in characterising ion currents, parameterising models, as well as being a challenging test of assumptions made about ion channel gating.

Citation

Mirams, G. R., Clerx, M., Whittaker, D. G., & Lei, C. L. (2024). Optimal experimental designs for characterising ion channel gating by filling the phase-voltage space of model dynamics. Mathematics in Medical and Life Sciences, 2024(1), Article 2375494. https://doi.org/10.1080/29937574.2024.2375494

• Journal Article Type: Article
• Acceptance Date: Jun 19, 2024
• Online Publication Date: Jul 23, 2024
• Publication Date: Jul 23, 2024
• Deposit Date: Jul 2, 2024
• Publicly Available Date: Aug 9, 2024
• Journal: Mathematics in Medical and Life Sciences
• Electronic ISSN: 2993-7574
• Publisher: Taylor & Francis
• Peer Reviewed: Peer Reviewed
• Volume: 2024
• Issue: 1
• Article Number: 2375494
• DOI: https://doi.org/10.1080/29937574.2024.2375494
• Keywords: Experimental design; mathematical model; ion channel; electrophysiology; hERG
• Public URL: https://nottingham-repository.worktribe.com/output/34350633