title: Effects of Na+Current and Mechanogated Channels in Myofibroblasts on Myocyte Excitability and Repolarization.
abstract: Fibrotic remodeling, characterized by fibroblast phenotype switching, is often associated with atrial fibrillation and heart failure. This study aimed to investigate the effects on electrotonic myofibroblast-myocyte (Mfb-M) coupling on cardiac myocytes excitability and repolarization of the voltage-gated sodium channels (VGSCs) and single mechanogated channels (MGCs) in human atrial Mfbs. Mathematical modeling was developed from a combination of (1) models of the human atrial myocyte (including the stretch activated ion channel current,ISAC) and Mfb and (2) our formulation of currents through VGSCs (INa_Mfb) and MGCs (IMGC_Mfb) based upon experimental findings. The effects of changes in the intercellular coupling conductance, the number of coupled Mfbs, and the basic cycle length on the myocyte action potential were simulated. The results demonstrated that the integration ofISAC,INa_Mfb, andIMGC_Mfbreduced the amplitude of the myocyte membrane potential (Vmax) and the action potential duration (APD), increased the depolarization of the resting myocyte membrane potential (Vrest), and made it easy to trigger spontaneous excitement in myocytes. For Mfbs, significant electrotonic depolarizations were exhibited with the addition ofINa_MfbandIMGC_Mfb. Our results indicated thatISAC,INa_Mfb, andIMGC_Mfbsignificantly influenced myocytes and Mfbs properties and should be considered in future cardiac pathological mathematical modeling.
authors.affiliation: Department of Information Technology, Hainan Medical University, Haikou 571199, China.
authors.forename: Heqing
authors.identifier: 0000-0002-3571-2695
authors.initials: H
authors.lastname: Zhan
authors.affiliation: Cardiac Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing 100037, China.
authors.forename: Jingtao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Information Technology, Hainan Medical University, Haikou 571199, China.
authors.forename: Jialun
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Information Technology, Hainan Medical University, Haikou 571199, China.
authors.forename: Guilai
authors.initials: G
authors.lastname: Han
mesh_terms: D000200:Action Potentials; D003198:Computer Simulation; D006325:Heart Atria / Q000473:pathology; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D008465:Mechanoreceptors / Q000502:physiology*; D008564:Membrane Potentials; D008955:Models, Cardiovascular; D032342:Muscle Cells / Q000166:cytology*; D058628:Myofibroblasts / Q000166:cytology*; D012964:Sodium / Q000737:chemistry*
chemical_list: D007473:Ion Channels; D012964:Sodium