Feasibility of Estimating Maximum Ion Conductance Parameters from the Shape of the Action Potential. A Simulation Study

Abstract

metabolic sink, but only when the sink exceeds a critical size (r>0.4cm). Phase singularity analysis indicates that the fibrillatory activity is initiated at sites close the border zone. The results emphasize the power of integrating cellular electrophysiological, Ca2þ handling, and metabolic subsystems into a multiscale model to simulate emergent macroscopic phenomena in the heart. Moreover, the results provide a proof-of-concept of the metabolic sink hypothesis and a new tool to study its role in arrhythmogenesis and sudden cardiac death.

Perspectives on Scaffold Designs with Roles in Liver Cell Asymmetry and Medical and Industrial Applications by Using a New Type of Specialized 3D Bioprinter

“…This stage of researchdevelopment, which involves a relatively small number of cells, is imperative to understand the variables described as the intermediate stage in the realization of artificial organs with a high number of cells, such as in the case of the kidney. In this case, there are extremely complex signaling mechanisms at the level of ion channels [70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87] (which must be individually identified at the initial stage) and ion pumps, which require a multitude of cell types.…”

Novel Automated Patch-clamp Assays on Stem Cell-derived Cardiomyocytes: Will they Standardize In Vitro Pharmacology and Arrhythmia Research?

“…Thus, evidence of a pharmacological effect at the level of AP (FP or whole-cell) in spontaneous or induced pacing conditions represents only the first step in a complex process of arrhythmogenic mechanism assessment for that compound. In a simulation study performed with the LuoRudy dynamic model [20], using a large database of 45,000 APs generated with variable combinations of ion current surface densities, in the range of 0.25-2 times the default value, scanned against a test action potential obtained by modifying a single current component, we have shown that the simple AP shape matching criterion does not lead to a unique unambiguous identification of the modified current component [21]. The whole-cell patch-clamp approach offers superior versatility compared to both optical and MEA-based screening assays, 60 40 20 0 -20 -40 -60 -80 80 60 40 20 0 -20 -40 -60 80 60 40 20 0 -20 -40 -60 2800 2600 2400 2200 2000 1800 1600 1400 1200 1000 800 600 400 between subcellular compartments during an AP [25].…”