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2020 - Assessment of the Effects of Online Linear Leak Current Compensation at Different Pacing Frequencies in a Dynamic Action Potential Clamp System

icon pl Patchliner publication in Computing in Cardiology (2020)

Authors:
Fabbri A., Prins A., de Boer T.P.

Journal:
Computing in Cardiology (2020)


Abstract:

Dynamic action potential (AP) clamp (dAPC) is an electrophysiology technique that allows one to study in real time the effects of a biological current included in a computational AP model. During an experiment, the seal resistance between the cell membrane and the pipette is finite and a leak current (Ileak) occurs. Its reduction is crucial to properly assess the effect of a drug. Our work aims to quantify the impact of Ileak on a ventricular AP model and to evaluate the benefits of an online compensation. We carried out the experiments using a prototype Nanion Patchliner Dynamite8 in dAPC mode, running the ten Tusscher human ventricular AP model. We use a passive model cell (Cm = 19.8pF, Rseal = 500MOhm) and online compensate the leak current adopting a linear model. Vmax, RMP and AP D20,50,90 are measured at several degrees of compensation (within 0 and 100%), at different pacing frequencies (0.5, 1, 2 Hz), and compared with the AP model in the open loop condition (i.e. with no connection between the model cell and the AP model). Ileak decreases Vmax, depolarizes RMP (up to +6.1mV at 1 Hz ) and prolongs AP D both during the plateau and the late repolarization; a full compensation of Ileak brings the AP biomarkers close to the open loop condition. With this test, we show that online compensation of Ileak is beneficial for proper assessment of AP biomarker. The correction of f RMP is key, as it affects the following phases of the AP.


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