scholarly journals Effects of Serum Calcium Changes on the Cardiac Action Potential and the ECG in a Computational Model

2018 ◽  
Vol 4 (1) ◽  
pp. 251-254 ◽  
Author(s):  
María Hernández Mesa ◽  
Nicolas Pilia ◽  
Olaf Dössel ◽  
Stefano Severi ◽  
Axel Loewe
Keyword(s):  
Action Potential ◽  
Computational Model ◽  
Cell Model ◽  
Cellular Level ◽  
Calcium Dependent ◽  
Cardiac Action ◽  
Dependent Inactivation ◽  
End Stage ◽  
Extracellular Sodium ◽  
Ventricular Cell Model

AbstractPatients suffering from end stage of chronic kidney disease (CKD) often undergo haemodialysis to normalize the electrolyte concentrations. Moreover, cardiovascular disease (CVD) is the main cause of death in CKD patients. To study the connection between CKD and CVD, we investigated the effects of an electrolyte variation on cardiac signals (action potential and ECG) using a computational model. In a first step, simulations with the Himeno et al. ventricular cell model were performed on cellular level with different extracellular sodium ([Na+]o), calcium ([Ca2+]o) and potassium ([K+]o) concentrations as occurs in CKD patients. [Ca2+]o and [K+]o changes caused variations in different features describing the morphology of the AP. Changes due to a [Na+]o variation were not as prominent. Simulations with [Ca2+]o variations were also carried out on ventricular ECG level and a 12-lead ECG was computed. Thus, a multiscale simulator from ion channel to ECG reproducing the calcium-dependent inactivation of ICaL was achieved. The results on cellular and ventricular level agree with results from literature. Moreover, we suggest novel features representing electrolyte changes that have not been described in literature. These results could be helpful for further studies aiming at the estimation of ionic concentrations based on ECG recordings.

A model of beta-adrenergic effects on calcium and potassium current in bullfrog atrial myocytes

1991 ◽  
Vol 261 (6) ◽  
pp. H1937-H1944
Author(s):  
J. M. Shumaker ◽  
J. W. Clark ◽  
W. R. Giles
Keyword(s):  
Action Potential ◽  
Potassium Current ◽  
Beta Adrenergic ◽  
Calcium Dependent ◽  
Dependent Inactivation ◽  
Atrial Myocyte ◽  
Muscarinic Cholinergic ◽  
High Doses ◽  
Dose Dependent ◽  
Cholinergic Effects

A model of beta-adrenergic and muscarinic cholinergic effects on the bullfrog atrial myocyte has been developed to simulate the dose-dependent effects of isoprenaline (Iso) on the action potential duration (APD); i.e., low doses of Iso lengthen the APD, whereas high doses shorten the APD. In this model, the reduction in APD is the result of 1) calcium-dependent inactivation of calcium current (ICa) resulting from the enhancement of ICa by Iso and 2) an enhancement of potassium current (IK) due to both an Iso-induced increase in the rate of activation of IK and an increase in peak action potential height. The effect of acetylcholine (ACh) is simulated by a reduction in the Iso-induced increase in ICa and IK through a reduction in relative adenosine 3',5'-cyclic monophosphate concentration ([cAMP]), as well as activation of the ACh-sensitive potassium current. At low [Iso] levels in the presence of a high [ACh], the muscarinic cholinergic effects dominate the beta-adrenergic change. However, for a large [Iso] and a small [ACh], this pattern of changes in transmembrane currents is different; in this case the model predicts that ACh can actually increase APD.

scholarly journals Action potential conduction between a ventricular cell model and an isolated ventricular cell

1996 ◽  
Vol 70 (1) ◽  
pp. 281-295 ◽  
Author(s):  
R. Wilders ◽  
R. Kumar ◽  
R.W. Joyner ◽  
H.J. Jongsma ◽  
E.E. Verheijck ◽  
...  
Keyword(s):  
Action Potential ◽  
Cell Model ◽  
Ventricular Cell ◽  
Ventricular Cell Model

scholarly journals Adaptation of the Calcium-dependent Tension Development in Ventricular Cardiomyocytes

2021 ◽  
Vol 7 (2) ◽  
pp. 251-254
Author(s):  
Stephanie Appel ◽  
Tobias Gerach ◽  
Olaf Dössel ◽  
Axel Loewe
Keyword(s):  
Cell Model ◽  
Calcium Transient ◽  
Cellular Level ◽  
Tension Development ◽  
Ventricular Cell ◽  
Calcium Dependent ◽  
Active Contraction ◽  
Cardiac Electromechanics ◽  
Maximum Relative Deviation ◽  
Isometric Twitch

Abstract Today a variety of models describe the physiological behavior of the heart on a cellular level. The intracellular calcium concentration plays an important role, since it is the main driver for the active contraction of the heart. Due to different implementations of the calcium dynamics, simulating cardiac electromechanics can lead to severely different behaviors of the active tension when coupling the same tension model with different electrophysiological models. To handle these variations, we present an optimization tool that adapts the parameters of the most recent, human based tension model. The goal is to generate a physiologically valid tension development when coupled to an electrophysiological cellular model independent of the specifics of that model's calcium transient. In this work, we focus on a ventricular cell model. In order to identify the calcium-sensitive parameters, a sensitivity analysis of the tension model was carried out. In a further step, the cell model was adapted to reproduce the sarcomere length-dependent behavior of troponin C. With a maximum relative deviation of 20.3% per defined characteristic of the tension development, satisfactory results could be obtained for isometric twitch tension. Considering the length-dependent troponin handling, physiological behavior could be reproduced. In conclusion, we propose an algorithm to adapt the tension development model to any calcium transient input to achieve a physiologically valid active contraction on a cellular level. As a proof of concept, the algorithm is successfully applied to one of the most recent human ventricular cell models. This is an important step towards fully coupled electromechanical heart models, which are a valuable tool in personalized health care.

scholarly journals Genetic Ablation of NCX1.1 Na+-dependent Inactivation Impacts Cardiac Action Potential and Ca2+ Transient

2020 ◽  
Vol 118 (3) ◽  
pp. 100a
Author(s):  
Federica Steccanella ◽  
Kyle Scranton ◽  
Namuna Panday ◽  
Marina Angelini ◽  
Rui Zhang ◽  
...  
Keyword(s):  
Action Potential ◽  
Cardiac Action Potential ◽  
Genetic Ablation ◽  
Cardiac Action ◽  
Dependent Inactivation

scholarly journals A CACNA1A variant associated with trigeminal neuralgia alters the gating of Cav2.1 channels

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Eder Gambeta ◽  
Maria A. Gandini ◽  
Ivana A. Souza ◽  
Laurent Ferron ◽  
Gerald W. Zamponi
Keyword(s):  
Trigeminal Neuralgia ◽  
Missense Mutation ◽  
Neurotransmitter Release ◽  
Trigeminal System ◽  
Wild Type ◽  
Calcium Dependent ◽  
Whole Cell Patch Clamp ◽  
C Terminus ◽  
Dependent Inactivation

AbstractA novel missense mutation in the CACNA1A gene that encodes the pore forming α1 subunit of the CaV2.1 voltage-gated calcium channel was identified in a patient with trigeminal neuralgia. This mutation leads to a substitution of proline 2455 by histidine (P2455H) in the distal C-terminus region of the channel. Due to the well characterized role of this channel in neurotransmitter release, our aim was to characterize the biophysical properties of the P2455H variant in heterologously expressed CaV2.1 channels. Whole-cell patch clamp recordings of wild type and mutant CaV2.1 channels expressed in tsA-201 cells reveal that the mutation mediates a depolarizing shift in the voltage-dependence of activation and inactivation. Moreover, the P2455H mutant strongly reduced calcium-dependent inactivation of the channel that is consistent with an overall gain of function. Hence, the P2455H CaV2.1 missense mutation alters the gating properties of the channel, suggesting that associated changes in CaV2.1-dependent synaptic communication in the trigeminal system may contribute to the development of trigeminal neuralgia.

Sign in / Sign up

Export Citation Format

Share Document