Human Purkinje in silico model enables mechanistic investigations into automaticity and pro-arrhythmic abnormalities
Cardiac Purkinje cells (PCs) are implicated in lethal arrhythmias caused by cardiac diseases, mutations, and drug action. However, the pro-arrhythmic mechanisms in PCs are not entirely understood, particularly in humans, as most investigations are conducted in animals. The aims of this study are to...
Elmentve itt :
| Szerzők: | |
|---|---|
| Dokumentumtípus: | Cikk |
| Megjelent: |
2020
|
| Sorozat: | JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
142 |
| doi: | 10.1016/j.yjmcc.2020.04.001 |
| mtmt: | 31287102 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/19501 |
| LEADER | 02729nab a2200277 i 4500 | ||
|---|---|---|---|
| 001 | publ19501 | ||
| 005 | 20200915091405.0 | ||
| 008 | 200915s2020 hu o 0|| zxx d | ||
| 022 | |a 0022-2828 | ||
| 024 | 7 | |a 10.1016/j.yjmcc.2020.04.001 |2 doi | |
| 024 | 7 | |a 31287102 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
| 041 | |a zxx | ||
| 100 | 1 | |a Trovato Cristian | |
| 245 | 1 | 0 | |a Human Purkinje in silico model enables mechanistic investigations into automaticity and pro-arrhythmic abnormalities |h [elektronikus dokumentum] / |c Trovato Cristian |
| 260 | |c 2020 | ||
| 300 | |a 24-38 | ||
| 490 | 0 | |a JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY |v 142 | |
| 520 | 3 | |a Cardiac Purkinje cells (PCs) are implicated in lethal arrhythmias caused by cardiac diseases, mutations, and drug action. However, the pro-arrhythmic mechanisms in PCs are not entirely understood, particularly in humans, as most investigations are conducted in animals. The aims of this study are to present a novel human PCs electrophysiology biophysically-detailed computational model, and to disentangle ionic mechanisms of human Purkinje-related electrophysiology, pacemaker activity and arrhythmogenicity. The new Trovato2020 model incorporates detailed Purkinje-specific ionic currents and Ca2+ handling, and was developed, calibrated and validated using human experimental data acquired at multiple frequencies, both in control conditions and following drug application. Multiscale investigations were performed in a Purkinje cell, in fibre and using an experimentally-calibrated population of PCs to evaluate biological variability. Simulations demonstrate the human Purkinje Trovato2020 model is the first one to yield: (i) all key AP features consistent with human Purkinje recordings; (ii) Automaticity with funny current up-regulation (iii) EADs at slow pacing and with 85% hERG block; (iv) DADs following fast pacing; (v) conduction velocity of 160 cm/s in a Purkinje fibre, as reported in human. The human in silico PCs population highlights that: (1) EADs are caused by ICaL reactivation in PCs with large inward currents; (2) DADs and triggered APs occur in PCs experiencing Ca2+ accumulation, at fast pacing, caused by large L-type calcium current and small Na+/Ca2+ exchanger. The novel human Purkinje model unlocks further investigations into the role of cardiac Purkinje in ventricular arrhythmias through computer modeling and multiscale simulations. | |
| 700 | 0 | 1 | |a Passini Elisa |e aut |
| 700 | 0 | 1 | |a Nagy Norbert |e aut |
| 700 | 0 | 1 | |a Varró András |e aut |
| 700 | 0 | 2 | |a Abi-Gerges Najah |e aut |
| 700 | 0 | 2 | |a Severi Stefano |e aut |
| 700 | 0 | 2 | |a Rodriguez Blanca |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/19501/1/31287102.pdf |z Dokumentum-elérés |