GAUR, Namit; HOF, Thomas; HAÏSSAGUERRE, Michel; VIGMOND, Edward

doi:10.1016/j.bpj.2018.11.3137

Métadonnées

Afficher la notice complète

Licence d’utilisation du document

http://creativecommons.org/licenses/by-nc/

GAUR, Namit
Université de Bordeaux [UB]
IHU-LIRYC

HOF, Thomas
Université de Bordeaux [UB]
IHU-LIRYC

HAÏSSAGUERRE, Michel
IHU-LIRYC

Langue

Article de revue

Ce document a été publié dans

Biophysical Journal. 2019-02, vol. 116, n° 3, p. 469-476

Biophysical Society

Résumé en anglais

Transient receptor potential melastatin member 4 (TRPM4) channels are nonselective monovalent cationic channels found in human atria and conduction system. Overexpression of TRPM4 channels has been found in families suffering from inherited cardiac arrhythmias, notably heart block. In this study, we integrate a mathematical formulation of the TRPM4 channel into a Purkinje cell model (Pan-Rudy model). Instead of simply adding the channel to the model, a combination of existing currents equivalent to the TRPM4 current was constructed, based on TRPM4 current dynamics. The equivalent current was then replaced by the TRPM4 current to preserve the model action potential. Single-cell behavior showed early afterdepolarizations for increases in TRPM4 channel expression above twofold. In a homogeneous strand of tissue, propagation conducted faithfully for lower expression levels but failed completely for more than a doubling of TRPM4 channel expression. Only with a heterogeneous distribution of channel expression was intermittent heart block seen. This study suggests that in Purkinje fibers, TRPM4 channels may account for sodium background current (INab), and that a heterogeneous expression of TRPM4 channels in the His/Purkinje system is required for type II heart block, as seen clinically.< Réduire

Métadonnées

Partager cette publication !

Licence d’utilisation du document

Propagation Failure by TRPM4 Overexpression

Langue

Ce document a été publié dans

Résumé en anglais

URI

DOI

Origine

Unités de recherche