Department of Pharmacology

 

SparkMaster 2 (SM2)

  SM2 is a new user-friendly software for accurate analysis of Ca sparks in line-scan images. It enables detecting multiple distinct types of Ca release events (sparks, waves, etc.) and characterizes their individual properties, such as amplitude, width, duration, time constant of decay etc. It can process data from a range of cell types, such as ventricular and atrial myocytes, as well as smooth muscle cells. It can process data collected across different experimental conditions, including imaging of permeabilized, as well as of intact electrically stimulated cells.

Below are provided links to runnable versions of the software for multiple operating systems (no installation needed), test data, and user guide:

README, User guide, Test data

Windows version

MacOS version and instructions for starting it for the first time

Linux version

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LabHEART

  LabHEART is a very user-friendly interactive computer model of integrated Cardiac Myocyte ion channel and Ca transport. It is useful for both students and researchers to understand the cardiac action potential, ion channel properties and Ca transients.

Click Here to Download Lab Heart Installer
Computer Simulation of Cardiac Myocyte

Click Here to Download Lab Axon Installer
Computer Simulation of the Giant Squid Axion

 

MaxChelator

  MaxChelator is an easy to use program to calculate complex ionic solutions (e.g. using Ca-EGTA-Mg-ATP etc). That is, if you need to make a solution with a specific free [Ca] and [Mg] and include Ca buffers like EGTA, EDTA, BAPTA... this will tell you how much total Ca, EGTA... to use to achieve it. The software was written by Chris Patton (Stanford) and this link is to his site

Click here to Download MaxChelator

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Shannon-Bers Rabbit Ventricular Model

The Shannon-Bers Model is an integrated mathematical model of cardiac excitation-contraction coupling, focusing on detailed Ca handling with four compartments of junctional cleft, subsarcolemmal space, cytosolic bulk, and sarcoplasmic reticulum. It is especially helpful for scientific researcher to verify and predict experimental results.

The Matlab code of the model is available for download here:

Matlab code

The CellML model was created by Martin Fink of Oxford University using COR (Cellular Open Resource) and this link is to the CellML website:

http://models.cellml.org/exposure/d72a36fe0b7e121068c96bcb1ff6044a/shannon_wang_puglisi_weber_bers_2004_a.cellml/view

 

Grandi-Pasqualini-Bers Human Ventricular Model

The Grandi-Pasqualini-Bers Model was developed within the framework of the Shannon-Bers rabbit ventricular model and based on experimental data obtained in human ventricular myocytes.

The Matlab code of the model is available for download here:

Click Here to Download

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Grandi et al. Human Atrial Model

The Grandi et al. Model was developed by incorporating the experimentally known atrio-ventricular differences into the Grandi-Pasqualini-Bers human ventricular model. Parameters were also tuned to recapitulate action potential and Ca handling characteristics of chronic atrial fibrillation.
The Matlab code of sinus rhythm and atrial fibrillation models is available for download here:

Click Here to Download

 

SparkMaster

SparkMaster is a plugin for ImageJ which allows rapid and reliable Ca spark analysis in line scan images. The underlying analysis algorithm is adapted from the threshold-based standard method of spark analysis developed by Cheng et al. (Biophys J 1999;76:606-17). SparkMaster offers a graphical user interface through which all analysis parameters and output options are selected. The analysis includes general image parameters (number of detected sparks, spark frequency) as well as individual spark parameters (Amplitude, FWHM, FDHM, Full Width, Full Duration, Time-to-Peak, maximum steepness of spark upstroke, time constant of spark decay). Please see our paper in AJP-Cell, 2007 for details.

Click Here to Download SparkMaster

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Morotti-Grandi-Bers Rabbit Ventricular Model

The Morotti-Grandi-Bers model was developed integrating a modified version of the L-type Ca current (LTCC) model by Mahajan et al. (Biophys J. 2008 Jan 15;94(2):392-410) into the framework of the Shannon-Bers rabbit ventricular model (available for download on this website). The LTCC model was extended to reflect more faithfully contributions of CDI and VDI to total inactivation.

Click Here to Download - Simulink Model

Click Here to Download - Matlab Model

 

Morotti et al. Mouse Ventricular Model

The Morotti et al. model describes excitation-contraction coupling in the mouse ventricular myocyte with integrated descriptions of Ca, Ca/calmodulin-dependent protein kinase II (CaMKII) and protein kinase A signaling pathways. This model was built upon the Soltis and Saucerman rabbit ventricular model (Biophys J. 2010 Oct 6;99(7):2038-47) and incorporates the experimentally known differences in mouse vs. rabbit electrophysiology, Ca handling, and kinase signaling and target phosphorylation. Model parameters were also tuned to recapitulate the electrophysiologic changes during chronic (transgenic) CaMKII overexpression.

Click Here to Download - Matlab Code

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Negroni et al. Model of Myofilament Contraction in Rabbit Ventricular Myocytes

The Negroni et al. model describes excitation-contraction coupling in the rabbit ventricular myocytes. A new model of myofilament contraction is here included into an established (and updated) computational framework, which integrates descriptions of electrophysiology, Ca and Na handling (from Shannon et al. Biophys J. 2004 Nov;87(5):3351-71), Ca/calmodulin-dependent protein kinase II (CaMKII) and protein kinase A (PKA) signaling pathways (from Soltis and Saucerman, Biophys J. 2010 Oct 6;99(7):2038-47).

Click Here to Download

 

Morotti et al. Human Atrial I_Na Model

Morotti et al. integrated a Na current Markov model (Grandi et al. Biophys J. 2007;93:3835-47, and Wagner et al. Circ Arrhythm Electrophysiol. 2009;2:285-94) into the framework of the Grandi-Bers human atrial model (Circ Res. 2011;109:1055-66, available for download on this website). The Na current model was extended to reproduce the dose-dependent effect of the Na channel blocker ranolazine (as in Moreno et al. Circ Res. 2013;113:e50-61).

Click Here to Download - Matlab Code

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Morotti et al. code for logistic regression analysis of populations of electrophysiological models 2017

This package contains the code used to investigate proarrythmic mechanisms on a population of electrophysiological models with the method of multivariable logistic regression. In this example, the Morotti et al. model of human atrial myocyte (J Mol Cell Cardiol. 2016 Jul;96:63-71, available for download on this website) is used to create a family of 1000 model variants by perturbing model parameters, and to simulate an electrophysiological protocol that enhances EAD proclivity. Logistic regression analysis allows relating changes in model parameters to the presence/absence of EADs.

Click Here to Download - Matlab Code

 

Bartos et al. model of IKs in rabbit ventricular myocytes 2017

The Bartos et al. model was developed modifying the formulation of the delayed rectifier K current IKs in the parent model developed by Negroni et et al. (J Mol Cell Cardiol. 2015 Apr;81:162-75, available for download on this website). The new formulation reproduces the Ca2+-dependent regulation of IKs experimentally observed.

Click Here to Download - Matlab Code

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Morotti et al. code for linear regression analysis of populations of electrophysiological models.

This package contains the Matlab code used to perform sensitivity analysis on a population of electrophysiological models with the method of linear logistic regression. Here, the Kapela et al. model of rat mesenteric smooth muscle cell (Journal of Theoretical Biology 253 (2008) 238– 260) is used to create a family of 1000 model variants by perturbing model parameters, and to investigate how model parameters influence membrane potential and calcium concentration.

Click Here to Download - Matlab Code

 

Mouse Ventricular Model with Myofilament Contraction

The Morotti et al. model of mouse ventricular myocyte (J Physiol. 2014 Mar 15;592(6):1181-97, available for download on this website) is here modified to integrate the Negroni et al. model of myofilament contraction (J Mol Cell Cardiol. 2015 Apr;81:162-75, see rabbit model available for download on this website). This model was developed to investigate the compartmentalization of cAMP/PKA signaling in Surdo et al. Nat Commun. 2017.

Click Here to Download - Matlab Code

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MarkoLAB simulator (MATLAB platform)

MarkoLAB provides an original way of visualizing the stochastic behavior of a channel. It clarifies concepts, such as recovery from inactivation, calcium- versus voltage-dependent inactivation, and tail currents. It is not restricted to ionic channels only but it can be extended to other transporters, such as exchangers and pumps. This program is intended as a didactical tool to illustrate the dynamical behavior of a channel. It has been implemented in two platforms MATLAB® and LabVIEW® to enhance the target users of this new didactical tool. The computational cost of implementing a stochastic simulation is within the range of a personal computer performance; making MarkoLAB suitable to be run during a lecture or presentation.
To install the MarkoLAB simulator (MATLAB platform) click the links below:

MarkoLAB simulator (MATLAB platform)

 

Ellinwood et al. Human Atrial Model 2017 (new Markov-type IKur model)

Ellinwood et al. integrated a Markov-type model of the IKur current derived from Zhou et al. (PLoS ONE 2012; e42295), modified to fit voltage-clamp data from human atrial myocytes, into the Morotti et al. human atrial model (J Mol Cell Cardiol. 2016 Jul; 96:63-71, available for download on this webpage). The IKur current model was extended to reproduce dose-dependent drug binding to various conformational states of the channel with variable affinity and binding kinetics.

Click Here to Download - Matlab Code