Modelling the Effect of Intracellular Calcium in the Rundown of L-Type Calcium Current

Agrawal, Aditi; Clerx, Michael; Wang, Ken; Polonchuk, Liudmila; Gavaghan, David J.; Mirams, Gary R.

Abstract

The L-type calcium current (ICaL) is a key current of the heart playing an important role in the contraction of the cardiomyocyte. Patch-clamp recordings of ionic currents can be associated with a reduction of the current magnitude with time (termed 'rundown'), and this phenomenon is particularly pronounced for ICaL recordings. Some part of rundown can be attributed to the unique sensitivity of L-type calcium channels (LCCs) to local [Ca2+]. In this paper, we study the experimental conditions in which rundown due to calcium-dependent inactivation (CDI) is minimised. We use first principles to derive an analytical equation for the diffusion of a calcium-chelating buffer from a patch hole on the cell's surface to the entirety of the cell. This determines the concentration profile of the buffer with respect to time and space. We then use the equation to simulate the effects of incoming calcium via the LCCs and its chemical reaction with the buffer.

• Conference Name: 2022 Computing in Cardiology Conference
• Conference Location: Tampere, Finland
• Start Date: Sep 4, 2022
• End Date: Sep 7, 2022
• Acceptance Date: Jun 13, 2022
• Online Publication Date: Apr 3, 2023
• Publication Date: 2022
• Deposit Date: Oct 13, 2023
• Publicly Available Date: Nov 28, 2023
• Publisher: Institute of Electrical and Electronics Engineers
• Volume: 2022-September
• Book Title: 2022 Computing in Cardiology (CinC)
• ISBN: 9798350310139
• DOI: https://doi.org/10.22489/CinC.2022.051
• Public URL: https://nottingham-repository.worktribe.com/output/20008089
• Publisher URL: https://ieeexplore.ieee.org/document/10081742