Título: Tx, TqNet and Ttriang Values

Autor: Llopis Lorente, Jordi; Gomis-Tena Dolz, Julio; Cano García, Jordi; Romero Pérez, Lucia; Saiz Rodríguez, Francisco Javier; Trénor Gomis, Beatriz Ana

Resumen: This repository contains the Matlab functions used in [1] and six Excel files named “Tx matrix KrKsCaL.xlsx”, “Tx matix KrNaLCaL.xlsx”, “TqNet matrix KrKsCaL.xlsx”, “TqNet matrix KrNaLCaL.xlsx”, "Ttirang matrix KrKsCaL.xlsx" and “Ttirang matrix KrNaLCaL.xlsx”. These files contain the value of three arrhythmogenic indices proposed in [1] (Tx, TqNet and Ttriang) resulting from simulations of drug effects on the action potential. The simulations were performed in a modified version of the O’Hara-Rudy model (ORd) [2] of human endocardial ventricular cells (492.536 simulations). References: [1]. Llopis J., Gomis-Tena J., Cano J., Romero L., Saiz J., Trenor B. In-Silico Classifiers for Assessment of Drug Proarrhythmicity. 2020 (Currently under revision) [2]. O’Hara, T.; Virág, L.; Varró, A.; Rudy, Y. Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation. PLoS Comput. Biol. 2011, 7 (5), e1002061.

Descripción: Every sheet in described files contains a table of numbers (doubles), resulting from the transformation of a three-dimensional matrix. To do so, the first three columns of each table contain the Coordinates x, y and z or z' of the original matrix respectively (no units). They range from -3 to 1.5. Coordinates were calculated as the logarithm of the ratio of a drug concentration (C) over the concentration that is required to inhibit a 50% of a given ion channel current (Half inhibitory concentration or IC50). They represent the block effect of such drug on four main currents which control the Action Potential shape and duration, namely, the rapid component of the potassium delayed rectifier current (IKr), the slow component of the potassium delayed rectifier current (IKs), the late sodium current (INaL) and the calcium type L current (ICaL). The following formulae can be used to deduce mentioned Coordinates: x = log_10(C/(IC_50 (I_Kr))) ; y = log_10(C/(IC_50 (I_CaL ) )); z = log_10(C/(IC_50 (I_CaL)); and z' = log_10(C/(IC_50 (I_NaL)). These are indeed part of the Hill equation (Hill coefficient set to 1), where G is the channel’s resulting conductance and G0 is the channel’s control conductance: G_[x || y || z || z'] = G_0·1/(1+C/(IC_(50, [x || y || z || z'] ) )) = G_0·1/(1+10^([x || y || z || z']) ). Conductances of the four main currents are thus translated into cardiac cellular or tissue models to study the effect of a wide range of drug concentrations. The following parameters were obtained and summarized in currently described files. Detailed methods of the performed simulations, as well as biomarker calculations, can be consulted in [1].

URI: http://hdl.handle.net/10251/136919

Fecha: 2020-02-14

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